Pregnancy, labour and delivery Flashcards

Question

What are the rules for starting the progestogen-only pill?

Answer 1

Starting the POP on day 1 to 5 of the menstrual cycle means the woman is protected immediately. It can be started at other times of the cycle provided pregnancy can be excluded. Additional contraception is required for 48 hours. It takes 48 hours for the cervical mucus to thicken enough to prevent sperm entering the uterus. The POP can be started even if there is a risk of pregnancy, as it is not known to be harmful in pregnancy. However, the woman should do a pregnancy test 3 weeks after the last unprotected intercourse. Emergency contraception before starting the pill may be considered if required. (The combined pill takes seven days before the woman is protected from pregnancy, as it works by inhibiting ovulation rather than thickening the cervical mucus. Therefore, additional contraception is required for 48 hours with the POP and seven days with the COCP when starting after day 5 of the menstrual cycle. Both can be started within the first 5 days of the menstrual cycle and work immediately, as it is very unlikely a woman will ovulate this early in the cycle.)

Answer 2

1. Switching between POPs POPs can be switched immediately without any need for extra contraception. 2. Switching from a COCP to a POP When switching from a COCP to a POP, the directions depend on what point they are in the COCP pill packet. They can start the POP immediately, without additional contraception, if they: -Have taken the COCP consistently for more than 7 days (they are in week 2 or 3 of the pill pack) -Are on days 1-2 of the hormone-free period following a full pack of the COCP The rules for days 3-7 of the hormone-free period and days 1-7 of taking the COCP depend on whether they have had unprotected sex since day 3 of the hormone-free period. -If they have not had unprotected sex since day 3 of the hormone-free period, they can start the POP immediately but require additional contraception (e.g., condoms) for the first 48 hours of taking the POP. - If they have had unprotected sex since day 3 of the hormone-free period, they should take the COCP until they have taken 7 days consecutively, after which they can switch over to the POP without any additional requirements. Theoretically, taking the COCP for 7 consecutive days inhibits ovulation for the next 7 days. The POP does not reliably prevent ovulation and works mainly by thickening the cervical mucous. Sperm can live for 5 days in the uterus. Therefore, if the woman has unprotected sex on day 3 or later of the hormone-free period after taking the COCP, sperm can enter the uterus and live there for 5 days (until the 8th day after finishing the COCP). Taking the POP during this time will make no difference to the sperm already in the uterus, as they are already past the cervix. Then, if the woman ovulates on the 8th day after finishing the COCP, those sperm are there waiting to fertilise the egg.

Answer 3

Changes to the bleeding schedule is one of the primary adverse effects of the progestogen-only pill. Unscheduled bleeding is common in the first three months and often settles after that. Where the irregular bleeding is persistent (for longer than 3 months), other causes need to be excluded (e.g. STIs, pregnancy or cancer). Approximately: -20% have no bleeding (amenorrhoea) -40% have regular bleeding -40% have irregular, prolonged or troublesome bleeding Other side effects include: -Breast tenderness -Headaches -Acne There is also an increased risk of: -Ovarian cysts -Small risk of ectopic pregnancy with traditional POPs (not desogestrel) due to reduce ciliary action in the tubes -Minimal increased risk of breast cancer, returning to normal ten years after stopping

Answer 4

A pill is classed as “missed” if it is: -More than 3 hours late for a traditional POP (more than 26 hours after the last pill) -More than 12 hours late for the desogestrel-POP (more than 36 hours after the last pill) The instructions are to take a pill as soon as possible, continue with the next pill at the usual time (even if this means taking two in 24 hours) and use extra contraception for the next 48 hours of regular use. Emergency contraception is required if they have had sex since missing the pill or within 48 hours of restarting the regular pills. Episodes of diarrhoea or vomiting are managed as “missed pills”, and extra contraception (i.e. condoms) is required until 48 hours after the diarrhoea and vomiting settle.

Answer 5

The progestogen-only injection is also known as depot medroxyprogesterone acetate (DMPA). It is given at 12 to 13 week intervals as an intramuscular or subcutaneous injection of medroxyprogesterone acetate (a type of progestin). The DMPA is more than 99% effective with perfect use, but less effective with typical use (94%). It is less effective with typical use because women may forget to book in for an injection every 12 to 13 weeks. There are two versions commonly used in the UK, all containing medroxyprogesterone acetate: 1. Depo-Provera: given by intramuscular injection 2. Sayana Press: a subcutaneous injection device that can be self-injected by the patient Noristerat is an alternative to the DMPA that contains norethisterone and works for eight weeks. This is usually used as a short term interim contraception (e.g. after the partner has a vasectomy) rather than a long term solution.

Answer 6

UK MEC 4: Active breast cancer UK MEC 3: -Ischaemic heart disease and stroke -Unexplained vaginal bleeding -Severe liver cirrhosis -Liver cancer The DMPA can cause osteoporosis. This is something to consider in older women and patients on steroids for asthma or inflammatory conditions. It is UK MEC 2 in women over 45 years, and women should generally switch to an alternative by age 50 years. It can take 12 months for fertility to return after stopping the injections, making it less suitable for women who may wish to get pregnant in the near term.

Answer 7

The main action of the depot injection is to inhibit ovulation. It does this by inhibiting FSH secretion by the pituitary gland, preventing the development of follicles in the ovaries. Additionally, the depot injection works by: -Thickening cervical mucus -Altering the endometrium and making it less accepting of implantation

Answer 8

Starting on day 1 to 5 of the menstrual cycle offers immediate protection, and no extra contraception is required. Starting after day 5 of the menstrual cycle requires seven days of extra contraception (e.g. condoms) before the injection becomes reliably effective. Women need to have injections every 12 – 13 weeks. Delaying past 13 weeks creates a risk of pregnancy.

Answer 9

Changes to the bleeding schedule is one of the primary considerations with progestogen-only contraception. Bleeding often becomes more irregular, and in some women, it may be heavier and last longer. This is usually temporary, and after a year of regular use, most women will stop bleeding altogether (amenorrhoea). It is not possible to predict how individuals will respond. - Alternative causes need to be excluded where problematic bleeding continues, including a sexual health screen, pregnancy test and ensuring cervical screening is up to date. -The FSRH guidelines suggest taking the combined oral contraceptive pill (COCP) in addition to the injection for three months when problematic bleeding occurs, to help settle the bleeding. -Another option is a short course (5 days) of mefenamic acid to halt the bleeding. Other side effects include: -Weight gain -Acne -Reduced libido -Mood changes -Headaches -Flushes -Hair loss (alopecia) -Skin reactions at injection sites Reduced bone mineral density (osteoporosis) is an important side effect of the depot injection. Oestrogen helps maintain bone mineral density in women, and is mainly produced by the follicles in the ovaries. Suppressing the development of follicles reduces the amount of oestrogen produced, and this can lead to decreased bone mineral density. The depot injection may be associated with a very small increased risk of breast and cervical cancer. (The two side effects that are unique to the progestogen injection are weight gain and osteoporosis. These adverse effects are not associated with any other forms of contraception)

Answer 10

There are several possible benefits of the injection, with evidence that it: -Improves dysmenorrhoea (painful periods) -Improves endometriosis-related symptoms -Reduces the risk of ovarian and endometrial cancer -Reduces the severity of sickle cell crisis in patients with sickle cell anaemia

Answer 11

The progestogen-only implant is a small (4cm) flexible plastic rod that is placed in the upper arm, beneath the skin and above the subcutaneous fat. It slowly releases progestogen into the systemic circulation. It lasts for three years and then needs replacing. The progestogen-only implant is more than 99% effective with perfect and typical use. Once in place, there is no room for user error. It needs to be replaced every three years to remain effective. The progestogen-only implant has very few contraindications and risks. The only UKMEC 4 criteria for the implant is active breast cancer. Nexplanon is the implant used in the UK. It contains 68mg of etonogestrel. It is licensed for use between the ages of 18 and 40 years. Mechanism The progestogen-only implant works by: -Inhibiting ovulation -Thickening cervical mucus -Altering the endometrium and making it less accepting of implantation

Answer 12

Inserting the implant on day 1 to 5 of the menstrual cycle provides immediate protection. Insertion after day 5 of the menstrual cycle requires seven days of extra contraception (e.g. condoms), similar to the injection. Specific qualifications are required to insert the implant. It is inserted one-third the way up the upper arm, on the medial side. Local anaesthetic (lidocaine) is used prior to inserting the implant. A specially designed device is used to insert the implant horizontally, beneath the skin and above the subcutaneous fat. It should be palpable immediately after insertion. Pressing on one end of the implant should make the other end pop upwards against the skin. Specific qualifications are also required to remove the implant. Lidocaine is used as a local anaesthetic. The device is located, and a small incision is made in the skin at one end. The device is removed using pressure on the other end or forceps. Contraception is required immediately after it has been removed (but not immediately before).

Answer 13

-Effective and reliable contraception -It can improve dysmenorrhoea (painful menstruation) -It can make periods lighter or stop all together -No need to remember to take pills (just remember to change the device every three years) -It does not cause weight gain (unlike the depo injection) -No effect on bone mineral density (unlike the depo injection) -No increase in thrombosis risk (unlike the COCP) -No restrictions for use in obese patients (unlike the COCP)

Answer 14

Several factors may limit the appeal of the implant: -It requires a minor operation with a local anaesthetic to insert and remove the device -It can lead to worsening of acne -There is no protection against sexually transmitted infections -It can cause problematic bleeding: 1/3 have infrequent bleeding, 1/4 have frequent or prolonged bleeding, 1/5 have no bleeding, The remainder have normal regular bleeds (Problematic bleeding is managed similarly to the progestogen-only implant. The FSRH guidelines suggest the combined oral contraceptive pill (COCP) in addition to the implant for three months when problematic bleeding occurs, to help settle the bleeding (provided there are no contraindications).) -Implants can be bent or fractured -Implants can become impalpable or deeply implanted, leading to investigations and additional management: Women are advised to palpate the implant occasionally, and if it becomes impalpable, extra contraception is required until it is located. An ultrasound or xray may be required to locate an impalpable implant. They may need referral to a specialist removal centre. The manufacturer of Nexplanon adds barium sulphate to make it radio-opaque so that it can be seen on xrays. In very rare cases there are reports of devices entering blood vessels and migrating through the body, including to the lungs. If the implant cannot be located even after an ultrasound scan, a chest xray may be considered to identify an implant in a pulmonary artery.

Answer 15

Coils are devices inserted into the uterus that provide contraception. They are a form of long-acting reversible contraception. Once fitted, they work for a long time. Removing the device restores fertility. There are two types of intrauterine device (IUD): 1. Copper coil (Cu-IUD): contains copper and creates a hostile environment for pregnancy 2. Levonorgestrel intrauterine system (LNG-IUS): contains progestogen that is slowly released into the uterus Both types of coil are more than 99% effective when properly inserted. Fertility returns immediately after removal of an intrauterine device. Often, the two types of coils are referred to as IUD and IUS. The intrauterine device (IUD) refers to the copper coil, and the intrauterine system (IUS) refers to the levonorgestrel (e.g. Mirena) coil. The copper coil is just a “device”, whereas the hormones in the Mirena make it a “system”.

Answer 16

-Pelvic inflammatory disease or infection -Immunosuppression -Pregnancy -Unexplained bleeding -Pelvic cancer -Uterine cavity distortion (e.g. by fibroids)

Answer 17

In women at increased risk of sexually transmitted infections (e.g. under 25 years old), screening for chlamydia and gonorrhoea is performed before insertion of a coil. Specific qualifications are required to insert the implant. A bimanual is performed before the procedure to check the position and size of the uterus. A speculum is inserted, and specialised equipment is used to fit the device. Forceps can be used to stabilise the cervix while the device is inserted. Blood pressure and heart rate are recorded before and after insertion. There may be some temporary crampy period type pain after insertion. NSAIDs may be used to help with discomfort after the procedure. Women need to be seen 3 to 6 weeks after insertion to check the threads. They should be taught to feel the strings to ensure the coil remains in place. Risks relating to the insertion of the coil include: -Bleeding -Pain on insertion -Vasovagal reactions (dizziness, bradycardia and arrhythmias) -Uterine perforation (1 in 1000, higher in breastfeeding women) -Pelvic inflammatory disease (particularly in the first 20 days) -The expulsion rate is highest in the first three months

Answer 18

When the coil threads cannot be seen or palpated, three things need to be excluded: 1. Expulsion 2. Pregnancy 3. Uterine perforation Extra contraception (i.e. condoms) is required until the coil is located. The first investigation is an ultrasound. An abdominal and pelvic xray can be used to look for a coil elsewhere in the abdomen or peritoneal cavity after a uterine perforation. Hysteroscopy or laparoscopic surgery may be required depending on the location of the coil.

Answer 19

Before the coil is removed, women need to abstain from sex or use condoms for 7 days, or there is a risk of pregnancy. The strings are located and slowly pulled to remove the device.

Answer 20

The copper coil (IUD) is a long-acting reversible contraception licensed for 5 – 10 years after insertion (depending on the device). It can also be used as emergency contraception, inserted up to 5 days after an episode of unprotected intercourse. It is notably contraindicated in Wilson’s disease. Mechanism Copper is toxic to the ovum and sperm. It also alters the endometrium and makes it less accepting of implantation.

Answer 21

-Reliable contraception -It can be inserted at any time in the menstrual cycle and is effective immediately -It contains no hormones, so it is safe for women at risk of VTE or with a history of hormone-related cancers -It may reduce the risk of endometrial and cervical cancer

Answer 22

-A procedure is required to insert and remove the coil, with associated risks -It can cause heavy or intermenstrual bleeding (this often settles) -Some women experience pelvic pain -It does not protect against sexually transmitted infections -Increased risk of ectopic pregnancies -Intrauterine devices can occasionally fall out (around 5%) The copper coil is contraindicated in Wilson’s disease. Wilson’s disease is a condition where there is excessive accumulation of copper in the body and tissues.

Answer 23

There are four types of IUS you may come across, all containing levonorgestrel: 1. Mirena: effective for 5 years for contraception, and also licensed for menorrhagia and HRT 2. Levosert: effective for 5 years, and also licensed for menorrhagia 3. Kyleena: effective for 5 years 4. Jaydess: effective for 3 years The Mirena coil is commonly used for contraception, menorrhagia and endometrial protection for women on HRT. It is licensed for 5 years for contraception, but only 4 years for HRT.

Answer 24

The LNG-IUS works by releasing levonorgestrel (progestogen) into the local area: -Thickening cervical mucus -Altering the endometrium and making it less accepting of implantation -Inhibiting ovulation in a small number of women The LNG-IUS can be inserted up to day 7 of the menstrual cycle without any need for additional contraception. If it is inserted after day 7, pregnancy needs to be reasonably excluded, and extra protection (i.e. condoms) is required for 7 days.

Answer 25

-It can make periods lighter or stop altogether -It may improve dysmenorrhoea or pelvic pain related to endometriosis -No effect on bone mineral density (unlike the depo injection) -No increase in thrombosis risk (unlike the COCP) -No restrictions for use in obese patients (unlike the COCP) -The Mirena has additional uses (i.e. HRT and menorrhagia)

Answer 26

-A procedure is required to insert and remove the coil, with associated risks -It can cause spotting or irregular bleeding -Some women experience pelvic pain -It does not protect against sexually transmitted infections -Increased risk of ectopic pregnancies -Increased incidence of ovarian cysts -There can be systemic absorption causing side effects of acne, headaches, or breast tenderness -Intrauterine devices can occasionally fall out (around 5%) Problematic bleeding Irregular bleeding can occur, particularly in the first six months. This usually settles with time. Alternative causes need to be excluded where problematic bleeding continues, including a sexual health screen, pregnancy test and ensuring cervical screening is up to date. The FSRH guidelines suggest taking the combined oral contraceptive pill (COCP) in addition to the LNG-IUS for three months when problematic bleeding occurs, to help settle the bleeding. Actinomyces-Like Organisms (ALO) on Smears Actinomyces-like organisms are often discovered incidentally during smear tests in women with an intrauterine device (coil). These do not require treatment unless they are symptomatic. Where the woman is symptomatic (e.g. pelvic pain or abnormal bleeding), removal of the intrauterine device may be considered.

Answer 27

Emergency contraception can be used after episodes of unprotected sexual intercourse (UPSI). This includes situations where the contraceptive method is not protective, such as damaged condoms or multiple missed pills. There are three options for emergency contraception: 1. Levonorgestrel should be taken within 72 hours of UPSI 2. Ulipristal should be taken within 120 hours of UPSI 3. Copper coil can be inserted within 5 days of UPSI, or within 5 days of the estimated date of ovulation

Answer 28

The copper coil is the most effective. It is also not affected by BMI, enzyme-inducing drugs or malabsorption, all of which can significantly reduce the effectiveness of oral methods. With oral emergency contraception, the sooner it is taken, the more effective it is. Oral emergency contraception is unlikely to be effective after ovulation has occurred; however, it is offered after UPSI on any day of the menstrual cycle. The woman needs to take a pregnancy test if her period is delayed. Oral emergency contraception does not protect against further episodes of UPSI. Both levonorgestrel and ulipristal can be used more than once in a menstrual cycle. Other things to consider when starting emergency contraception: -Reassure about confidentiality -Sexually transmitted infections -Future contraception plans -Safeguarding, rape and abuse

Answer 29

The copper coil can be used as an emergency contraception up to 5 days after unprotected intercourse, or within 5 days after the earliest estimated date of ovulation. Ovulation occurs 14 days before the end of the cycle, so if a woman’s shortest cycle length is 28 days, the earliest estimated date of ovulation is day 14. It would be day 12 for a 26-day cycle, or day 16 for a 30-day cycle. The copper coil is toxic to the ovum and sperm, and also inhibits implantation. It is the most effective emergency contraception, being over 99% effective. The FSRH guidelines (2017) advised offering the copper coil first line for emergency contraception. Insertion may lead to pelvic inflammatory disease, particularly in women that are high risk of sexually transmitted infections. Consider empirical treatment of pelvic infections where the risk is higher. The coil should be kept in until at least the next period, after which it can be removed. Alternatively, it can be left in long-term as contraception.

Answer 30

Levonorgestrel is a type of progestogen. It works by preventing or delaying ovulation. It is the same hormone found in the intrauterine system (hormonal coil). It is not known to be harmful to the pregnancy if pregnancy does occur. The combined pill or progestogen-only pill can be started immediately after taking levonorgestrel. Extra contraception (i.e. condoms) is required for the first 7 days of the combined pill or the first 2 days of the progestogen-only pill. Levonorgestrel is licensed for use up to 72 hours post intercourse. The dose listed in the BNF is: -1.5mg as a single dose -3mg as a single dose in women above 70kg or BMI above 26 Nausea and vomiting are common side effects. If vomiting occurs within 3 hours of taking the pill, the dose should be repeated. Other side effects include: -Spotting and changes to the next menstrual period -Diarrhoea -Breast tenderness -Dizziness -Depressed mood Levonorgestrel is not known to be harmful when breastfeeding, and breastfeeding can continue (unlikely ulipristal). The NICE CKS advise that breastfeeding is avoided for 8 hours after taking the dose to reduce the exposure to the infant.

Answer 31

Ulipristal acetate is a selective progesterone receptor modulator (SERM) that works by delaying ovulation. The common brand name is EllaOne. It is more effective than levonorgestrel. It is not known to be harmful if pregnancy does occur; however, there is limited data on this. Wait 5 days before starting the combined pill or progestogen-only pill after taking ulipristal. Extra contraception (ie. condoms) is required for the first 7 days of the combined pill or the first 2 days of the progestogen-only pill. It is given as a single dose (30mg) to prevent pregnancy after unprotected intercourse. Ulipristal is licensed for use up to 120 hours after intercourse. Nausea and vomiting are common side effects. If vomiting occurs within 3 hours of taking the pill, the dose should be repeated. Other side effects include: -Spotting and changes to the next menstrual period -Abdominal or pelvic pain -Back pain -Mood changes -Headache -Dizziness -Breast tenderness There are several notably restrictions with ulipristal: -Breastfeeding should be avoided for 1 week after taking ulipristal (milk should be expressed and discarded) -Ulipristal should be avoided in patients with severe asthma

Answer 32

Sterilisation procedures are permanent surgical interventions to prevent conception. It is essential to thoroughly counsel patients about the permanence of the procedure, and ensure they have made a fully informed decision. Sterilisation does not protect against sexually transmitted infections. The NHS does not provide reversal procedures. Private reversal procedures are available, but the success rate is low. Therefore, sterilisation should be considered permanent. Women: Tubal Occlusion The female sterilisation procedure is called tubal occlusion. This is typically performed by laparoscopy under general anaesthesia, with occlusion of the tubes using “Filshie clips”. Alternatively, the fallopian tubes can be tied and cut, or removed altogether. This can be done as an elective procedure, or during a caesarean section. The procedure works by preventing the ovum (egg) travelling from the ovary to the uterus along the fallopian tube. This means the ovum and sperm will not meet, and pregnancy cannot occur. The procedure is more than 99% effective (1 in 200 failure rate). Alternative contraception is required until the next menstrual period, as an ovum may have already reached the uterus during that cycle, ready for fertilisation. 2. Men: Vasectomy The male sterilisation procedure is called a vasectomy. This involves cutting the vas deferens, preventing sperm travelling from the testes to join the ejaculated fluid. This prevents sperm from being released into the vagina, preventing pregnancy. It is more than 99% effective (1 in 2000 failure rate). The procedure is performed under local anaesthetic and is relatively quick (15 – 20 minutes). This makes it a less invasive procedure than female sterilisation and often a better option for couples that are considering permanent means of contraception. Alternative contraception is required for two months after the procedure. Testing of the semen to confirm the absence of sperm is necessary before it can be relied upon for contraception. Semen testing is usually carried out around 12 weeks after the procedure, as it takes time for sperm that are still in the tubes to be cleared. A second semen analysis may be required for confirmation.

Answer 33

Gillick competence refers to a judgement about whether the understanding and intelligence of the child is sufficient to consent to treatment. Gillick competence needs to be assessed on a decision by decision basis, checking whether the child understands the implications of the treatment. Consent needs to be given voluntarily. When prescribing contraception to children under 16 years, it is essential to assess for coercion or pressure, for example, coercion by an older partner. This might raise safeguarding concerns.

Answer 34

The Frazer guidelines are specific guidelines for providing contraception to patients under 16 years without having parental input and consent. The House of Lords established these guidelines in 1985. To follow the guidelines, they need to meet the following criteria: 1. They are mature and intelligent enough to understand the treatment 2. They can’t be persuaded to discuss it with their parents or let the health professional discuss it 3. They are likely to have intercourse regardless of treatment 4. Their physical or mental health is likely to suffer without treatment 5. Treatment is in their best interest 6. Children should be encouraged to inform their parents, but if they decline and meet the criteria for Gillick competence and the Frazer guidelines, confidentiality can be kept.

Answer 35

85% will conceive within a year of regular unprotected sex. 1 in 7 couples will struggle to conceive naturally. Investigation and referral for infertility should be initiated after the couple has been trying to conceive without success for 12 months. This can be reduced to 6 months if the woman is older than 35, as her ovarian stores are likely to be already reduced and time is more precious.

Answer 36

1. Sperm problems (30%) 2. Ovulation problems (25%) 3. Tubal problems (15%) 4. Uterine problems (10%) 5. Unexplained (20%) 40% of infertile couples have a mix of male and female causes.

Answer 37

There is some general lifestyle advice for couples trying to get pregnant: 1. The woman should be taking 400mcg folic acid daily 2. Aim for a healthy BMI 3. Avoid smoking and drinking excessive alcohol 4. Reduce stress as this may negatively affect libido and the relationship 5. Aim for intercourse every 2 – 3 days 6. Avoid timing intercourse Timed intercourse to coincide with ovulation is not necessary or recommended as it can lead to increased stress and pressure in the relationship.

Answer 38

Initial investigations, often performed in primary care: -Body mass index (BMI) (low could indicate anovulation, high could indicate PCOS) -Chlamydia screening -Semen analysis -Female hormonal testing (see below) -Rubella immunity in the mother Female hormone testing involves: 1. Serum LH and FSH on day 2 to 5 of the cycle *High FSH suggests poor ovarian reserve (the number of follicles that the woman has left in her ovaries). The pituitary gland is producing extra FSH in an attempt to stimulate follicular development. *High LH may suggest polycystic ovarian syndrome (PCOS). 2. Serum progesterone on day 21 of the cycle (or 7 days before the end of the cycle if not a 28-day cycle): A rise in progesterone on day 21 indicates that ovulation has occurred, and the corpus luteum has formed and started secreting progesterone. 3. Anti-Mullerian hormone: Anti-Mullerian hormone can be measured at any time during the cycle and is the most accurate marker of ovarian reserve. It is released by the granulosa cells in the follicles and falls as the eggs are depleted. A high level indicates a good ovarian reserve. 4. Thyroid function tests when symptoms are suggestive 5. Prolactin (hyperprolactinaemia is a cause of anovulation) when symptoms of galactorrhea or amenorrhoea Further investigations, often performed in secondary care: - Ultrasound pelvis to look for polycystic ovaries or any structural abnormalities in the uterus - Hysterosalpingogram to look at the patency of the fallopian tubes - Laparoscopy and dye test to look at the patency of the fallopian tubes, adhesions and endometriosis

Answer 39

A hysterosalpingogram is a type of scan used to assess the shape of the uterus and the patency of the fallopian tubes. Not only does it help with diagnosis of infertility, but it also has therapeutic benefit. It seems to increase the rate of conception without any other intervention. Tubal cannulation under xray guidance can be performed during the procedure to open up the tubes. A small tube is inserted into the cervix. A contrast medium is injected through the tube and fills the uterine cavity and fallopian tubes. Xray images are taken, and the contrast shows up on the xray giving an outline of the uterus and tubes. If the dye does not fill one of the tubes, this will be seen on an xray and suggests a tubal obstruction. There is a risk of infection with the procedure, and often antibiotics are given prophylactically for patients with dilated tubes or a history of pelvic infection. Screening for chlamydia and gonorrhoea should be done before the procedure.

Answer 40

The patient is admitted for laparoscopy. During the procedure, dye is injected into the uterus and should be seen entering the fallopian tubes and spilling out at the ends of the tubes. This will not be seen when there is tubal obstruction. During laparoscopy, the surgeon can also assess for endometriosis or pelvic adhesions and treat these.

Answer 41

The options when anovulation is the cause of infertility include: -Weight loss for overweight patients with PCOS can restore ovulation -Clomifene may be used to stimulate ovulation -Letrozole may be used instead of clomifene to stimulate ovulation (aromatase inhibitor with anti-oestrogen effects) - Gonadotropins may be used to stimulate ovulation in women resistant to clomifene - Ovarian drilling may be used in polycystic ovarian syndrome - Metformin may be used when there is insulin insensitivity and obesity (usually associated with PCOS) Clomifene is an anti-oestrogen (a selective oestrogen receptor modulator). It is given on days 2 to 6 of the menstrual cycle. It stops the negative feedback of oestrogen on the hypothalamus, resulting in a greater release of GnRH and subsequently FSH and LH. Ovarian drilling involves laparoscopic surgery. The surgeon punctures multiple holes in the ovaries using diathermy or laser therapy. This can improve the woman’s hormonal profile and result in regular ovulation and fertility.

Answer 42

Management of Tubal Factors The options for women with alterations to the fallopian tubes that prevent the ovum from reaching the sperm and uterus include: -Tubal cannulation during a hysterosalpingogram -Laparoscopy to remove adhesions or endometriosis -In vitro fertilisation (IVF) Management of Uterine Factors Surgery may be used to correct polyps, adhesions or structural abnormalities affecting fertility.

Answer 43

1. Surgical sperm retrieval is used when there is a blockage somewhere along the vas deferens preventing sperm from reaching the ejaculated semen. A needle and syringe is used to collect sperm directly from the epididymis through the scrotum. 2. Surgical correction of an obstruction in the vas deferens may restore male fertility. 3. Intra-uterine insemination involves collecting and separating out high-quality sperm, then injecting them directly into the uterus to give them the best chance of success. It is unclear whether this is any better than normal intercourse. 4. Intracytoplasmic sperm injection (ICSI) involves injecting sperm directly into the cytoplasm of an egg. These fertilised eggs become embryos, and are injected into the uterus of the woman. This is useful when there are significant motility issues, a very low sperm count and other issues with the sperm. 5. Donor insemination with sperm from a donor is another option for male factor infertility.

Answer 44

Men should be given clear instructions for providing a sample: - Abstain from ejaculation for at least 3 days and at most 7 days - Avoid hot baths, sauna and tight underwear during the lead up to providing a sample - Attempt to catch the full sample - Deliver the sample to the lab within 1 hour of ejaculation - Keep the sample warm (e.g. in underwear) before delivery

Answer 45

Several lifestyle factors may affect the results of semen analysis and the quality and quantity of sperm: - Hot baths - Tight underwear - Smoking - Alcohol - Raised BMI - Caffeine A repeat sample is indicated after 3 months in borderline results or earlier (2 – 4 weeks) with very abnormal results.

Answer 46

Normal results indicated by the World Health Organisation are: -Semen volume (more than 1.5ml) -Semen pH (greater than 7.2) -Concentration of sperm (more than 15 million per ml) -Total number of sperm (more than 39 million per sample) -Motility of sperm (more than 40% of sperm are mobile) -Vitality of sperm (more than 58% of sperm are active) -Percentage of normal sperm (more than 4%) 1. Polyspermia (or polyzoospermia) refers to a high number of sperm in the semen sample (more than 250 million per ml). 2. Normospermia (or normozoospermia) refers to normal characteristics of the sperm in the semen sample. 3. Oligospermia (or oligozoospermia) is a reduced number of sperm in the semen sample. It is classified as: *Mild oligospermia (10 to 15 million / ml) *Moderate oligospermia (5 to 10 million / ml) *Severe oligospermia (less than 5 million / ml) *Cryptozoospermia refers to very few sperm in the semen sample (less than 1 million / ml). 4. Azoospermia is the absence of sperm in the semen.

Answer 47

1. Pre-Testicular Causes Testosterone is necessary for sperm creation. The hypothalamo-pituitary-gonadal axis controls testosterone. Hypogonadotrophic hypogonadism (low LH and FSH resulting in low testosterone), can be due to: -Pathology of the pituitary gland or hypothalamus Suppression due to stress, chronic conditions or hyperprolactinaemia -Kallman syndrome 2. Testicular Causes Testicular damage from: -Mumps -Undescended testes -Trauma -Radiotherapy -Chemotherapy -Cancer Genetic or congenital disorders that result in defective or absent sperm production, such as: -Klinefelter syndrome -Y chromosome deletions -Sertoli cell-only syndrome -Anorchia (absent testes) 3. Post-Testicular Causes Obstruction preventing sperm being ejaculated can be caused by: - Damage to the testicle or vas deferens from trauma, surgery or cancer - Ejaculatory duct obstruction - Retrograde ejaculation - Scarring from epididymitis, for example, caused by chlamydia - Absence of the vas deferens (may be associated with cystic fibrosis) - Young’s syndrome (obstructive azoospermia, bronchiectasis and rhinosinusitis)

Answer 48

The initial steps for investigating abnormal semen analysis include a history, examination, repeat sample and ultrasound of the testes. Patients with abnormal semen results are referred to a urologist for further investigations. Further investigations that may be considered include: -Hormonal analysis with LH, FSH and testosterone levels -Genetic testing -Further imaging, such as transrectal ultrasound or MRI -Vasography, which involves injecting contrast into the vas deferens and performing xray to assess for obstruction -Testicular biopsy

Answer 49

Management depends on the underlying cause, and can involve: -Surgical sperm retrieval where there is obstruction -Surgical correction of an obstruction in the vas deferens -Intra-uterine insemination involves separating high-quality sperm, then injecting them into the uterus -Intracytoplasmic sperm injection (ICSI) involves injecting sperm directly into the cytoplasm of an egg -Donor insemination involves sperm from a donor

Answer 50

A cycle of IVF involves a single episode of ovarian stimulation and collection of oocytes (eggs). A single cycle may produce several embryos. Each of these embryos can be transferred separately in multiple attempts at pregnancy, all during one “cycle” of IVF. Embryos that are not used immediately may be frozen to be used at a later date. Frozen embryos can potentially be used years later, even after a successful pregnancy. 1. Suppression of the Natural Menstrual Cycle There are two protocols for the suppression of the natural menstrual cycle, preventing ovulation and ensuring the ovaries respond correctly to the gonadotropins (i.e. FSH). Suppression of the natural cycle involves either the use of GnRH agonists or GnRH antagonists. The choice between the GnRH agonist and GnRH antagonist protocol depends on individual factors. - For the GnRH agonist protocol, an injection of a GnRH agonist (e.g. goserelin) is given in the luteal phase of the menstrual cycle, around 7 days before the expected onset of the menstrual period (usually day 21 of the cycle). This initially stimulates the pituitary gland to secrete a large amount of FSH and LH. However, after this initial surge in FSH and LH, there is negative feedback to the hypothalamus, and the natural production of GnRH is suppressed. This causes suppression of the menstrual cycle. - For the GnRH antagonist protocol, daily subcutaneous injections of a GnRH antagonist (e.g. cetrorelix) are given, starting from day 5 – 6 of ovarian stimulation. This suppresses the body releasing LH and causing ovulation to occur. Without suppression of the natural gonadotropins (LH and FSH) using one of the above protocols, ovulation would occur and the follicles that are developing would be released before it is possible to collect them. 2. Ovarian Stimulation Ovarian stimulation involves using medications to promote the development of multiple follicles in the ovaries. This starts at the beginning of the menstrual cycle (usually day 2), with subcutaneous injections of follicle-stimulating hormone (FSH) over 10 to 14 days. The FSH stimulates the development of follicles, and this is closely monitored with regular transvaginal ultrasound scans. When enough follicles have developed to an adequate size (usually around 18 millimetres), the FSH is stopped, and an injection of human chorionic gonadotropin (hCG) is given. This injection of HCG is given 36 hours before collection of the eggs. The hCG works similarly to LH does naturally, and stimulates the final maturation of the follicles, ready for collection. This is referred to as a “trigger injection”. 3. Oocyte Collection The oocytes (eggs) are collected from the ovaries under the guidance of a transvaginal ultrasound scan. A needle is inserted through the vaginal wall into each ovary to aspirate the fluid from each follicle. This fluid contains the mature oocytes from the follicles. The procedure is usually performed under sedation (not a general anaesthetic). The fluid from the follicles is examined under the microscope for oocytes.

Answer 51

1. Oocyte Insemination The male produces a semen sample around the time of oocyte collection. Frozen sperm from earlier samples may be used. The sperm and egg are mixed in a culture medium. Thousands of sperm need to be combined with each oocyte to produce enough enzymes (e.g. hyaluronic acid) for one sperm to penetrate the corona radiata and zona pellucida and fertilise the egg. *Intracytoplasmic Sperm Injection Intracytoplasmic sperm injection (ICSI) is a treatment used mainly for male factor infertility, where there are a reduced number or quality of sperm. It is an addition to the IVF process. After the eggs are harvested, and a semen sample is produced, the highest quality sperm are isolated and injected directly into the cytoplasm of the egg. 2. Embryo Culture Dishes containing the fertilised eggs are left in an incubator and observed over 2 – 5 days to see which will develop and grow. They are monitored until they reach the blastocyst stage of development (around day 5). 3. Embryo Transfer After 2 – 5 days, the highest quality embryos are selected for transfer. A catheter is inserted under ultrasound guidance through the cervix into the uterus. A single embryo is injected through the catheter into the uterus, and the catheter is removed. Generally, only a single embryo is transferred. Two embryos may be transferred in older women (i.e. over 35 years). Any remaining embryos can be frozen for future attempts at transfer. 4. Pregnancy A pregnancy test is performed around day 16 after egg collection. When this is positive, implantation has occurred. Even after a positive test, there is still the possibility of miscarriage or ectopic pregnancy. When the pregnancy test is negative, implantation has failed. At this point, hormonal treatment is stopped. The woman will go on to have a menstrual period. The bleeding may be more substantial than usual given the additional hormones used during ovarian stimulation. Progesterone is used from the time of oocyte collection until 8 – 10 weeks gestation, usually in the form of vaginal suppositories. This is to mimic the progesterone that would be released by the corpus luteum during a typical pregnancy. From 8 – 10 weeks the placenta takes over production of progesterone, and the suppositories are stopped. An ultrasound scan is performed early in the pregnancy (around 7 weeks) to check for a fetal heartbeat, and rule out miscarriage or ectopic pregnancy. When the ultrasound scan confirms a health pregnancy, the remainder of the pregnancy can proceed with standard care, as with any other pregnancy.

Answer 52

The main complications relating to the overall process are: -Failure -Multiple pregnancy -Ectopic pregnancy -Ovarian hyperstimulation syndrome There is a small risk of complications relating to the egg collection procedure: -Pain -Bleeding -Pelvic infection -Damage to the bladder or bowel

Answer 53

Ovarian hyperstimulation syndrome (OHSS) is a complication of ovarian stimulation during IVF infertility treatment. It is associated with the use of human chorionic gonadotropin (hCG) to mature the follicles during the final steps of ovarian stimulation.

Answer 54

The primary mechanism for OHSS is an increase in vascular endothelial growth factor (VEGF) released by the granulosa cells of the follicles. VEGF increases vascular permeability, causing fluid to leak from capillaries. Fluid moves from the intravascular space to the extravascular space. This results in oedema, ascites and hypovolaemia. The use of gonadotrophins (LH and FSH) during ovarian stimulation results in the development of multiple follicles. OHSS is provoked by the “trigger injection” of hCG 36 hours before oocyte collection. HCG stimulates the release of VEGF from the follicles. The features of the condition begin to develop after the hCG injection. There is also activation of the renin-angiotensin system. A notable finding in patients with OHSS is a raised renin level. The renin level correlates with the severity of the condition.

Answer 55

-Younger age -Lower BMI -Raised anti-Müllerian hormone -Higher antral follicle count -Polycystic ovarian syndrome -Raised oestrogen levels during ovarian stimulation

Answer 56

Women are individually assessed for their risk of developing OHSS. During stimulation with gonadotrophins, they are monitored with: -Serum oestrogen levels (higher levels indicate a higher risk) -Ultrasound monitor of the follicles (higher number and larger size indicate a higher risk) In women at higher risk several strategies may be used to reduce the risk: -Use of the GnRH antagonist protocol (rather than the GnRH agonist protocol) -Lower doses of gonadotrophins -Lower dose of the hCG injection -Alternatives to the hCG injection (i.e. a GnRH agonist or LH)

Answer 57

Early OHSS presents within 7 days of the hCG injection. Late OHSS presents from 10 days onwards. Features of the condition include: -Abdominal pain and bloating -Nausea and vomiting -Diarrhoea -Hypotension -Hypovolaemia -Ascites -Pleural effusions -Renal failure -Peritonitis from rupturing follicles releasing blood -Prothrombotic state (risk of DVT and PE)

Answer 58

The severity is determined based on the clinical features: 1. Mild: Abdominal pain and bloating 2. Moderate: Nausea and vomiting with ascites seen on ultrasound 3. Severe: Ascites, low urine output (oliguria), low serum albumin, high potassium and raised haematocrit (>45%) 4. Critical: Tense ascites, no urine output (anuria), thromboembolism and acute respiratory distress syndrome (ARDS)

Answer 59

Management is supportive with treatment of any complications. This involves: - Oral fluids - Monitoring of urine output - Low molecular weight heparin (to prevent thromboembolism) - Ascitic fluid removal (paracentesis) if required - IV colloids (e.g. human albumin solution) Patients with mild to moderate OHSS are often managed as an outpatient. Severe cases require admission, and critical cases may require admission to the intensive care unit (ICU). Haematocrit may be monitored to assess the volume of fluid in the intravascular space. Haematocrit is the concentration of red blood cells in the blood. When the haematocrit goes up, this indicates less fluid in the intravascular space, as the blood is becoming more concentrated. Raised haematocrit can indicate dehydration.

Answer 60

Ectopic pregnancy is when a pregnancy is implanted outside the uterus. The most common site is a fallopian tube. An ectopic pregnancy can also implant in the entrance to the fallopian tube (cornual region), ovary, cervix or abdomen.

Answer 61

Certain factors can increase the risk of ectopic pregnancy: -Previous ectopic pregnancy -Previous pelvic inflammatory disease -Previous surgery to the fallopian tubes -Intrauterine devices (coils) -Older age -Smoking

Answer 62

Ectopic pregnancy typically presents around 6 – 8 weeks gestation. Have a low threshold for suspecting an ectopic pregnancy, even in atypical presentations. Always ask about the possibility of pregnancy, missed periods and recent unprotected sex in women presenting with lower abdominal pain. The classic features of an ectopic pregnancy include: -Missed period -Constant lower abdominal pain in the right or left iliac fossa -Vaginal bleeding -Lower abdominal or pelvic tenderness -Cervical motion tenderness (pain when moving the cervix during a bimanual examination) It is also worth asking about: -Dizziness or syncope (blood loss) -Shoulder tip pain (peritonitis)

Answer 63

A transvaginal ultrasound scan is the investigation of choice for diagnosing a miscarriage. A gestational sac containing a yolk sac or fetal pole may be seen in a fallopian tube. Sometimes a non-specific mass may be seen in the tube. When a mass containing an empty gestational sac is seen, this may be referred to as the “blob sign”, “bagel sign” or “tubal ring sign” (all referring to the same appearance). A mass representing a tubal ectopic pregnancy moves separately to the ovary. The mass may look similar to a corpus luteum; however, a corpus luteum will move with the ovary. Features that may also indicate an ectopic pregnancy are: -An empty uterus -Fluid in the uterus, which may be mistaken as a gestational sac (“pseudogestational sac”)

Answer 64

A pregnancy of unknown location (PUL) is when the woman has a positive pregnancy test and there is no evidence of pregnancy on the ultrasound scan. In this scenario, an ectopic pregnancy cannot be excluded, and careful follow up needs to be in place until a diagnosis can be confirmed. Serum human chorionic gonadotropin (hCG) can be tracked over time to help monitor a pregnancy of unknown location. The serum hCG level is repeated after 48 hours, to measure the change from baseline. The developing syncytiotrophoblast of the pregnancy produces hCG. In an intrauterine pregnancy, the hCG will roughly double every 48 hours. This will not be the case in a miscarriage or ectopic pregnancy. A rise of more than 63% after 48 hours is likely to indicate an intrauterine pregnancy. A repeat ultrasound scan is required after 1 – 2 weeks to confirm an intrauterine pregnancy. A pregnancy should be visible on an ultrasound scan once the hCG level is above 1500 IU / l. A rise of less than 63% after 48 hours may indicate an ectopic pregnancy. When this happens the patient needs close monitoring and review. A fall of more than 50% is likely to indicate a miscarriage. A urine pregnancy test should be performed after 2 weeks to confirm the miscarriage is complete. Monitoring the clinical signs and symptoms is more important than tracking the hCG level, and any change in symptoms needs careful assessment.

Answer 65

Perform a pregnancy test in all women with abdominal or pelvic pain that may be caused by an ectopic pregnancy. Women with pelvic pain or tenderness and a positive pregnancy test need to be referred to an early pregnancy assessment unit (EPAU) or gynaecology service. All ectopic pregnancies need to be terminated. An ectopic pregnancy is not a viable pregnancy. There are three options for terminating an ectopic pregnancy: 1. Expectant management (awaiting natural termination) 2. Medical management (methotrexate) 3. Surgical management (salpingectomy or salpingotomy)

Answer 66

Criteria for expectant management: - Follow up needs to be possible to ensure successful termination - The ectopic needs to be unruptured - Adnexal mass < 35mm - No visible heartbeat - No significant pain - HCG level < 1500 IU / l Women with expectant management need careful follow up with close monitoring of hCG levels, and quick and easy access to services if their condition changes.

Answer 67

Criteria for methotrexate are the same as expectant management (Follow up needs to be possible to ensure successful termination, The ectopic needs to be unruptured, Adnexal mass < 35mm, No visible heartbeat, No significant pain), except: - HCG level must be < 5000 IU / l - There must be a confirmed absence of intrauterine pregnancy on ultrasound Methotrexate is highly teratogenic (harmful to pregnancy). It is given as an intramuscular injection into a buttock. This halts the progress of the pregnancy and results in spontaneous termination. Women treated with methotrexate are advised not to get pregnant for 3 months following treatment. This is because the harmful effects of methotrexate on pregnancy can last this long. Common side effects of methotrexate include: - Vaginal bleeding - Nausea and vomiting - Abdominal pain - Stomatitis (inflammation of the mouth)

Answer 68

Anyone that does not meet the criteria for expectant or medical management requires surgical management. Most patients with an ectopic pregnancy will require surgical management. This include those with: - Pain - Adnexal mass > 35mm - Visible heartbeat - HCG levels > 5000 IU / l There are two options for surgical management of ectopic pregnancy: 1. Laparoscopic salpingectomy 2. Laparoscopic salpingotomy Laparoscopic salpingectomy is the first-line treatment for ectopic pregnancy. This involves a general anaesthetic and key-hole surgery with removal of the affected fallopian tube, along with the ectopic pregnancy inside the tube. Laparoscopic salpingotomy may be used in women at increased risk of infertility due to damage to the other tube. The aim is to avoid removing the affected fallopian tube. A cut is made in the fallopian tube, the ectopic pregnancy is removed, and the tube is closed. There is an increased risk of failure to remove the ectopic pregnancy with salpingotomy compared with salpingectomy. NICE state up to 1 in 5 women having salpingotomy may need further treatment with methotrexate or salpingectomy. Anti-rhesus D prophylaxis is given to rhesus negative women having surgical management of ectopic pregnancy.

Answer 69

Miscarriage is the spontaneous termination of a pregnancy. 1. Early miscarriage is before 12 weeks gestation. 2. Late miscarriage is between 12 and 24 weeks gestation. There are several definitions to remember relating to miscarriage: - Missed miscarriage – the fetus is no longer alive, but no symptoms have occurred - Threatened miscarriage – vaginal bleeding with a closed cervix and a fetus that is alive - Inevitable miscarriage – vaginal bleeding with an open cervix - Incomplete miscarriage – retained products of conception remain in the uterus after the miscarriage - Complete miscarriage – a full miscarriage has occurred, and there are no products of conception left in the uterus - Anembryonic pregnancy – a gestational sac is present but contains no embryo

Answer 70

A transvaginal ultrasound scan is the investigation of choice for diagnosing a miscarriage. There are three key features that the sonographer looks for in an early pregnancy. These appear sequentially as the pregnancy develops. As each appears, the previous feature becomes less relevant in assessing the viability of the pregnancy. These features are: 1. Mean gestational sac diameter 2. Fetal pole and crown-rump length 3. Fetal heartbeat When a fetal heartbeat is visible, the pregnancy is considered viable. A fetal heartbeat is expected once the crown-rump length is 7mm or more. - When the crown-rump length is less than 7mm, without a fetal heartbeat, the scan is repeated after at least one week to ensure a heartbeat develops. - When there is a crown-rump length of 7mm or more, without a fetal heartbeat, the scan is repeated after one week before confirming a non-viable pregnancy. A fetal pole is expected once the mean gestational sac diameter is 25mm or more. When there is a mean gestational sac diameter of 25mm or more, without a fetal pole, the scan is repeated after one week before confirming an anembryonic pregnancy.

Answer 71

1. Less Than 6 Weeks Gestation Women with a pregnancy less than 6 weeks’ gestation presenting with bleeding can be managed expectantly provided they have no pain and no other complications or risk factors (e.g. previous ectopic). Expectant management before 6 weeks gestation involves awaiting the miscarriage without investigations or treatment. An ultrasound is unlikely to be helpful this early as the pregnancy will be too small to be seen. A repeat urine pregnancy test is performed after 7 – 10 days, and if negative, a miscarriage can be confirmed. When bleeding continues, or pain occurs, referral and further investigation is indicated. 2. More Than 6 Weeks Gestation Refer to an early pregnancy assessment service (EPAU) for women with a positive pregnancy test (more than 6 weeks’ gestation) and bleeding. Ultrasound will confirm the location and viability of the pregnancy. It is essential always to consider and exclude an ectopic pregnancy. There are three options for managing a miscarriage: 1. Expectant management (do nothing and await a spontaneous miscarriage) 2. Medical management (misoprostol) 3. Surgical management

Answer 72

Expectant management is offered first-line for women without risk factors for heavy bleeding or infection. 1 – 2 weeks are given to allow the miscarriage to occur spontaneously. A repeat urine pregnancy test should be performed three weeks after bleeding and pain settle to confirm the miscarriage is complete. Persistent or worsening bleeding requires further assessment and repeat ultrasound, as this may indicate an incomplete miscarriage and require additional management.

Answer 73

Misoprostol is a prostaglandin analogue, meaning it binds to prostaglandin receptors and activates them. Prostaglandins soften the cervix and stimulate uterine contractions. Medical management of miscarriage involves using a dose of misoprostol to expedite the process of miscarriage. This can be as a vaginal suppository or an oral dose. The key side effects of misoprostol are: 1. Heavier bleeding 2. Pain 3. Vomiting 4. Diarrhoea

Answer 74

Surgical management can be performed under local or general anaesthetic. There are two options for surgical management of a miscarriage: 1. Manual vacuum aspiration under local anaesthetic as an outpatient 2. Electric vacuum aspiration under general anaesthetic Prostaglandins (misoprostol) are given before surgical management to soften the cervix. 1. Manual vacuum aspiration involves a local anaesthetic applied to the cervix. A tube attached to a specially designed syringe is inserted through the cervix into the uterus. The person performing the procedure then manually uses the syringe to aspirate contents of the uterus. To consider manual vacuum aspiration, women must find the process acceptable and be below 10 weeks gestation. It is more appropriate for women that have previously given birth (parous women). 2. Electric vacuum aspiration is the traditional surgical management of miscarriage. It involves a general anaesthetic. The operation is performed through the vagina and cervix without any incisions. The cervix is gradually widened using dilators, and the products of conception are removed through the cervix using an electric-powered vacuum. Anti-rhesus D prophylaxis is given to rhesus negative women having surgical management of miscarriage.

Answer 75

An incomplete miscarriage occurs when retained products of conception (fetal or placental tissue) remain in the uterus after the miscarriage. Retained products create a risk of infection. There are two options for treating an incomplete miscarriage: 1. Medical management (misoprostol) 2. Surgical management (evacuation of retained products of conception) Evacuation of retained products of conception (ERPC) is a surgical procedure involving a general anaesthetic. The cervix is gradually widened using dilators, and the retained products are manually removed through the cervix using vacuum aspiration and curettage (scraping). A key complication is endometritis (infection of the endometrium) following the procedure.

Answer 76

Miscarriage is relatively common. Recurrent miscarriage is classed as three or more consecutive miscarriages. The risk of miscarriage increases with age, with the rate of miscarriage approximately: 10% in women aged 20 – 30 years 15% in women aged 30 – 35 years 25% in women aged 35 – 40 years 50% in women aged 40 – 45 years Investigations are initiated after: 1. Three or more first-trimester miscarriages 2. One or more second-trimester miscarriages

Answer 77

-Idiopathic (particularly in older women) -Antiphospholipid syndrome -Hereditary thrombophilias -Uterine abnormalities -Genetic factors in parents (e.g. balanced translocations in parental chromosomes) -Chronic histiocytic intervillositis -Other chronic diseases such as diabetes, untreated thyroid disease and systemic lupus erythematosus (SLE)

Answer 78

Antiphospholipid syndrome is a disorder associated with antiphospholipid antibodies, where blood becomes prone to clotting. The patient is in a hyper-coagulable state. The main associations are with thrombosis and complications in pregnancy, particularly recurrent miscarriage. Antiphospholipid syndrome can occur on its own, or secondary to an autoimmune condition such as systemic lupus erythematosus. The risk of miscarriage in patients with antiphospholipid syndrome is reduced by using both: - Low dose aspirin - Low molecular weight heparin (LMWH) Consider this in patients presenting with recurrent miscarriages. There may be a past history of deep vein thrombosis. Test for antiphospholipid antibodies, and treatment is with aspirin and LMWH.

Answer 79

The key inherited thrombophilias to remember are: 1. Factor V Leiden (most common) 2. Factor II (prothrombin) gene mutation 3. Protein S deficiency

Answer 80

Several uterine abnormalities can cause recurrent miscarriages: - Uterine septum (a partition through the uterus) - Unicornuate uterus (single-horned uterus) - Bicornuate uterus (heart-shaped uterus) - Didelphic uterus (double uterus) - Cervical insufficiency - Fibroids

Answer 81

Chronic histiocytic intervillositis is a rare cause of recurrent miscarriage, particularly in the second trimester. It can also lead to intrauterine growth restriction (IUGR) and intrauterine death. The condition is poorly understood. Histiocytes and macrophages build up in the placenta, causing inflammation and adverse outcomes. It is diagnosed by placental histology showing infiltrates of mononuclear cells in the intervillous spaces.

Answer 82

Patients should be referred to a specialist in recurrent miscarriage for further investigation. Investigations include: - Antiphospholipid antibodies - Testing for hereditary thrombophilias - Pelvic ultrasound - Genetic testing of the products of conception from the third or future miscarriages - Genetic testing on parents

Answer 83

The 1990 Human Fertilisation and Embryology Act altered and expanded the criteria for an abortion, and reduced the latest gestational age where an abortion is legal from 28 weeks to 24 weeks. An abortion can be performed before 24 weeks if continuing the pregnancy involves greater risk to the physical or mental health of: - The woman - Existing children of the family The threshold for when the risk of continuing the pregnancy outweighs the risk of terminating the pregnancy is a matter of clinical judgement and opinion of the medical practitioners. An abortion can be performed at any time during the pregnancy if: - Continuing the pregnancy is likely to risk the life of the woman - Terminating the pregnancy will prevent “grave permanent injury” to the physical or mental health of the woman - There is “substantial risk” that the child would suffer physical or mental abnormalities making it seriously handicapped The legal requirements for an abortion are: - Two registered medical practitioners must sign to agree abortion is indicated - It must be carried out by a registered medical practitioner in an NHS hospital or approved premise

Answer 84

Abortion services can be accessed by self-referral or by GP, GUM or family planning clinic referral. Doctors who object to abortions should pass on to another doctor able to make the referral. Many abortion services are accessed by self-referral, without the involvement of a GP or other doctor to make the referral. Marie Stopes UK is a charity that provides abortion services. They offer a remote service for women less than 10 weeks gestation, where consultations are held by telephone and medication are issued remotely to be taken at home. Women should be offered counselling and information to help decision making from a trained practitioner. Informed consent is essential.

Answer 85

A medical abortion is most appropriate earlier in pregnancy, but can be used at any gestation. It involves two treatments: 1. Mifepristone (anti-progestogen) 2. Misoprostol (prostaglandin analogue) 1 – 2 day later Mifepristone is an anti-progestogen medication that blocks the action of progesterone, halting the pregnancy and relaxing the cervix. Misoprostol is a prostaglandin analogue, meaning it binds to prostaglandin receptors and activates them. Prostaglandins soften the cervix and stimulate uterine contractions. From 10 weeks gestation, additional misoprostol doses (e.g. every 3 hours) are required until expulsion. Rhesus negative women with a gestational age of 10 weeks or above having a medical TOP should have anti-D prophylaxis.

Answer 86

Surgical abortion can be performed, depending on preference and gestational age, under: -Local anaesthetic -Local anaesthetic plus sedation -General anaesthetic Prior to surgical abortion, medications are used for cervical priming. This involves softening and dilating the cervix with misoprostol, mifepristone or osmotic dilators. Osmotic dilators are devices inserted into the cervix, that gradually expand as they absorb fluid, opening the cervical canal. There are two options for surgical abortion: 1. Cervical dilatation and suction of the contents of the uterus (usually up to 14 weeks) 2. Cervical dilatation and evacuation using forceps (between 14 and 24 weeks) Rhesus negative women having a surgical TOP should have anti-D prophylaxis.

Answer 87

Post-Abortion Care Women may experience vaginal bleeding and abdominal cramps intermittently for up to 2 weeks after the procedure. A urine pregnancy test is performed 3 weeks after the abortion to confirm it is complete. Contraception is discussed and started where appropriate. Support and counselling is offered. Complications: - Bleeding - Pain - Infection - Failure of the abortion (pregnancy continues) - Damage to the cervix, uterus or other structures

Answer 88

Nausea is a common symptom in pregnancy, particularly early on. Nausea and vomiting in pregnancy starts in the first trimester, peaking around 8 – 12 weeks gestation. The severe form of nausea and vomiting in pregnancy is called hyperemesis gravidarum. Nausea and vomiting are normal during early pregnancy. Symptoms usually start from 4 – 7 weeks, are worst around 10 – 12 weeks and resolve by 16 – 20 weeks. Symptoms can persist throughout pregnancy. The placenta produces human chorionic gonadotropin (hCG) during pregnancy. This hormone is thought to be responsible for nausea and vomiting. Theoretically, higher levels of hCG result in worse symptoms. Nausea and vomiting are more severe in molar pregnancies and multiple pregnancies due to the higher hCG levels. It also tends to be worse in the first pregnancy and overweight or obese women.

Answer 89

Hyperemesis gravidarum is the severe form of nausea and vomiting in pregnancy (NVP). The criteria for diagnosing hyperemesis gravidarum are “protracted” NVP plus: - More than 5% weight loss compared with before pregnancy - Dehydration - Electrolyte imbalance The severity can be assessed using the Pregnancy-Unique Quantification of Emesis (PUQE) score. This gives a score out of 15: < 7: Mild 7 – 12: Moderate > 12: Severe

Answer 90

Antiemetics are used to suppress nausea. Vaguely in order of preference and known safety, the choices are: 1. Prochlorperazine (stemetil) 2. Cyclizine 3. Ondansetron 4. Metoclopramide - Ranitidine or omeprazole can be used if acid reflux is a problem. The RCOG also suggest complementary therapies that may be considered by the woman: - Ginger - Acupressure on the wrist at the PC6 point (inner wrist) may improve symptoms Mild cases can be managed with oral antiemetics at home. Admission should be considered when: - Unable to tolerate oral antiemetics or keep down any fluids - More than 5 % weight loss compared with pre-pregnancy - Ketones are present in the urine on a urine dipstick (2 + ketones on the urine dipstick is significant) - Other medical conditions need treating that required admission Moderate-severe cases may require ambulatory care (e.g. early pregnancy assessment unit) or admission for: - IV or IM antiemetics - IV fluids (normal saline with added potassium chloride) - Daily monitoring of U&Es while having IV therapy - Thiamine (Vit B1) supplementation to prevent deficiency (prevents Wernicke-Korsakoff syndrome) - Thromboprophylaxis (TED stocking and low molecular weight heparin) during admission

Answer 91

A hydatidiform mole is a type of tumour that grows like a pregnancy inside the uterus. This is called a molar pregnancy. There are two types of molar pregnancy: a complete mole and a partial mole. A complete mole occurs when two sperm cells fertilise an ovum that contains no genetic material (an “empty ovum”). These sperm then combine genetic material, and the cells start to divide and grow into a tumour called a complete mole. No fetal material will form. A partial mole occurs when two sperm cells fertilise a normal ovum (containing genetic material) at the same time. The new cell now has three sets of chromosomes (it is a haploid cell). The cell divides and multiplies into a tumour called a partial mole. In a partial mole, some fetal material may form.

Answer 92

Molar pregnancy behaves like a normal pregnancy. Periods will stop and the hormonal changes of pregnancy will occur. There are a few things that can indicate a molar pregnancy versus a normal pregnancy: - More severe morning sickness - Vaginal bleeding - Increased enlargement of the uterus - Abnormally high hCG - Thyrotoxicosis (hCG can mimic TSH and stimulate the thyroid to produce excess T3 and T4) Ultrasound of the pelvis shows a characteristic “snowstorm appearance” of the pregnancy. Provisional diagnosis can be made by ultrasound and confirmed with histology of the mole after evacuation.

Answer 93

Management involves evacuation of the uterus to remove the mole. The products of conception need to be sent for histological examination to confirm a molar pregnancy. Patients should be referred to the gestational trophoblastic disease centre for management and follow up. The hCG levels are monitored until they return to normal. Occasionally the mole can metastasise, and the patient may require systemic chemotherapy.

Answer 94

Gravida (G) is the total number of pregnancies a woman has had Primigravida refers to a patient that is pregnant for the first time Multigravida refers to a patient that is pregnant for at least the second time Para (P) refers to the number of times the woman has given birth after 24 weeks gestation, regardless of whether the fetus was alive or stillborn Nulliparous (“nullip”) refers to a patient that has never given birth after 24 weeks gestation Primiparous technically refers to a patient that has given birth after 24 weeks gestation once before Multiparous (“multip”) refers to a patient that has given birth after 24 weeks gestation two or more times

Answer 95

The timeline for each pregnancy depends on the start date of the last menstrual period (LMP). This determines the gestational age (GA) and the estimated date of delivery (EDD) of the pregnancy. After the booking scan, the gestational age is more accurately assessed and the estimated date of delivery is updated accordingly. The gestational age is described in weeks and days. For example: 5 + 0 refers to 5 weeks gestational age (since the LMP) 13 + 6 refers to 13 weeks and 6 days gestational age

Answer 96

The first trimester is from the start of pregnancy until 12 weeks gestation. The second trimester is from 13 weeks until 26 weeks gestation. The third trimester is from 27 weeks gestation until birth. It is worth noting that fetal movements start from around 20 weeks gestation, and continue until birth.

Answer 97

1. Before 10 weeks: Booking clinic - Offer a baseline assessment and plan the pregnancy 2. Between 10 and 13 + 6: Dating scan - An accurate gestational age is calculated from the crown rump length (CRL), and multiple pregnancies are identified 3. 16 weeks: Routine Antenatal appointment - Discuss results and plan future appointments 4. Between 18 and 20 + 6: Anomaly scan - An ultrasound to identify any anomalies, such as heart conditions 5. 25, 28, 31, 34, 36, 38, 40, 41 and 42 weeks: Antenatal appointments - Monitor the pregnancy and discuss future plans

Answer 98

There may be additional appointments necessary if the woman fits certain criteria: - Additional appointments for higher risk or complicated pregnancies - Oral glucose tolerance test in women at risk of gestational diabetes (between 24 – 28 weeks) - Anti-D injections in rhesus negative women (at 28 and 34 weeks) - Ultrasound scan at 32 weeks for women with placenta praevia on the anomaly scan - Serial growth scans are offered to women at increased risk of fetal growth restriction

Answer 99

Several things are covered at each routine antenatal appointment: 1. Discuss plans for the remainder of the pregnancy and delivery 2. Symphysis–fundal height measurement from 24 weeks onwards 3. Fetal presentation assessment from 36 weeks onwards 4. Urine dipstick for protein for pre-eclampsia 5. Blood pressure for pre-eclampsia 6. Urine for microscopy and culture for asymptomatic bacteriuria

Answer 100

1. Whooping cough (pertussis) from 16 weeks gestation 2. Influenza (flu) when available in autumn or winter Live vaccines, such as the MMR vaccine, are avoided in pregnancy.

Answer 101

- Take folic acid 400mcg from before pregnancy to 12 weeks (reduces neural tube defects) - Take vitamin D supplement (10 mcg or 400 IU daily) - Avoid vitamin A supplements and eating liver or pate (vitamin A is teratogenic at high doses) - Don’t drink alcohol when pregnant (risk of fetal alcohol syndrome) - Don’t smoke (smoking has a long list of complications) - Avoid unpasteurised dairy or blue cheese (risk of listeriosis) - Avoid undercooked or raw poultry (risk of salmonella) - Continue moderate exercise but avoid contact sports - Sex is safe - Flying increases the risk of venous thromboembolism (VTE) - Place car seatbelts above and below the bump (not across it)

Answer 102

Alcohol can cross the placenta, enter the fetus, and disrupt fetal development. There is no safe level of alcohol in pregnancy. Pregnant women are encouraged not to drink alcohol at all. Small amounts are less likely to result in lasting effects. The effects are greatest in the first 3 months of pregnancy. Alcohol in early pregnancy can lead to: - Miscarriage - Small for dates - Preterm delivery - Fetal alcohol syndrome Fetal alcohol syndrome refers to certain characteristics that can occur in children of mothers that consumed alcohol during pregnancy. The features include: - Microcephaly (small head) - Thin upper lip - Smooth flat philtrum (the groove between the nose and upper lip) - Short palpebral fissure (short horizontal distance from one side of the eye to the other) - Learning disability - Behavioural difficulties - Hearing and vision problems - Cerebral palsy

Answer 103

Smoking in pregnancy increases the risk of: - Fetal growth restriction (FGR) - Miscarriage - Stillbirth - Preterm labour and delivery - Placental abruption - Pre-eclampsia - Cleft lip or palate - Sudden infant death syndrome (SIDS)

Answer 104

The RCOG advises flying is generally ok in uncomplicated healthy pregnancies up to: - 37 weeks in a single pregnancy - 32 weeks in a twin pregnancy After 28 weeks gestation, most airlines need a note from a midwife, GP or obstetrician to state the pregnancy is going well and there are no additional risks.

Answer 105

The booking clinic is the initial appointment to discuss the pregnancy and arrange plans for the pregnancy. This ideally occurs before 10 weeks gestation. The woman meets with a midwife to discuss all aspects of pregnancy. She will get a green book that documents the progress during the pregnancy. 1. Education Pregnancy-related topics are covered during the booking clinic: - What to expect at different stages of pregnancy - Lifestyle advice in pregnancy (e.g. not smoking) - Supplements (e.g. folic acid and vitamin D) - Plans for birth - Screening tests (e.g. Downs screening) - Antenatal classes - Breastfeeding classes - Discuss mental health 2. Booking Bloods A set of booking bloods are taken for: - Blood group, red cell autoantibodies and rhesus D status (Group and save) - Full blood count for anaemia - Screening for thalassaemia (all women) and sickle cell disease (women at higher risk) Patients are also offered screening for infectious diseases, by testing antibodies for: -HIV -Hepatitis B -Syphilis (Rubella no longer tested since 2016 due to good MMR vaccine) Screening for Down’s syndrome may be initiated depending on the gestational age. Bloods required for the combined test are taken from 11 weeks onwards. 3. Other Measures - Weight, height and BMI - Urine for protein and bacteria - Blood pressure - Discuss female genital mutilation - Discuss domestic violence 4. Risk Assessment Women are assessed for risk factors for other conditions, and plans are put in place with additional appointments booked. These conditions include: - Rhesus negative (book anti-D prophylaxis) - Gestational diabetes (book oral glucose tolerance test) - Fetal growth restriction (book additional growth scans) - Venous thromboembolism (provide prophylactic LMWH if high risk) - Pre-eclampsia (provide aspirin if high risk)

Answer 106

All women are offered screening for Down’s syndrome during pregnancy. The purpose of the screening test is to decide which women should receive more invasive tests to establish a definitive diagnosis. It is the choice of the woman whether to go ahead with screening. The screening tests involve taking measurements from the fetus using ultrasound, combining those measurements with the mother’s age and blood results and providing an indication of the risk of Down’s syndrome. Older mothers have a higher risk of Down’s syndrome.

Answer 107

1. Combined Test The combined test is the first line and the most accurate screening test. It is performed between 11 and 14 weeks gestation and involves combining results from ultrasound and maternal blood tests. Ultrasound measures nuchal translucency, which is the thickness of the back of the neck of the fetus. Down’s syndrome is one cause of a nuchal thickness greater than 6mm. Maternal blood tests: - Beta‑human chorionic gonadotrophin (beta-HCG) – a higher result indicates a greater risk - Pregnancy‑associated plasma protein‑A (PAPPA) – a lower result indicates a greater risk 2. Triple Test The triple test is performed between 14 and 20 weeks gestation. It only involves maternal blood tests: - Beta-HCG – a higher result indicates greater risk - Alpha-fetoprotein (AFP) – a lower result indicates a greater risk - Serum oestriol (female sex hormone) – a lower result indicates a greater risk 3. Quadruple Test The quadruple test is performed between 14 and 20 weeks gestation. It is identical to the triple test, but also includes maternal blood testing for inhibin-A. A higher inhibin-A indicates a greater risk. *The screening tests provide a risk score for the fetus having Down’s syndrome.*

Answer 108

The woman is offered amniocentesis or chorionic villus sampling. These tests involve taking a sample of the fetal cells to perform karyotyping for a definitive answer about Down’s: - Chorionic villus sampling (CVS) involves an ultrasound-guided biopsy of the placental tissue. This is used when testing is done earlier in pregnancy (before 15 weeks). - Amniocentesis involves ultrasound-guided aspiration of amniotic fluid using a needle and syringe. This is used later in pregnancy once there is enough amniotic fluid to make it safer to take a sample. *Non-Invasive Prenatal Testing Non-invasive prenatal testing (NIPT) is a relatively new test for detecting abnormalities in the fetus during pregnancy. It involves a simple blood test from the mother. The blood will contain fragments of DNA, some of which will come from the placental tissue and represent the fetal DNA. These fragments can be analysed to detect conditions such as Down’s. NIPT is not a definitive test, but it does give a very good indication of whether the fetus is affected. NIPT is gradually being rolled out in the NHS as an alternative to invasive testing (CVS and amniocentesis) for women that have a higher than 1 in 150 risk of Down’s syndrome.

Answer 109

Untreated or under-treated hypothyroidism in pregnancy can lead to several adverse pregnancy outcomes, including miscarriage, anaemia, small for gestational age and pre-eclampsia. Hypothyroidism is treated with levothyroxine (T4). Levothyroxine can cross the placenta and provide thyroid hormone to the developing fetus. The levothyroxine dose needs to be increased during pregnancy, usually by at least 25 – 50 mcg (30 – 50%). Treatment is titrated based on the TSH level, aiming for a low-normal TSH level.

Answer 110

Women with existing hypertension may need changes to their medications. Medications that should be stopped as they may cause congenital abnormalities: - ACE inhibitors (e.g. ramipril) - Angiotensin receptor blockers (e.g. losartan) - Thiazide and thiazide-like diuretics (e.g. indapamide) Medications that are not known to be harmful: - Labetalol (a beta-blocker – although other beta-blockers may have adverse effects) - Calcium channel blockers (e.g. nifedipine) - Alpha-blockers (e.g. doxazosin)

Answer 111

Women with epilepsy should take folic acid 5mg daily from before conception to reduce the risk of neural tube defects. Pregnancy may worsen seizure control due to the additional stress, lack of sleep, hormonal changes and altered medication regimes. Seizures are not known to be harmful to the pregnancy, other than the risk of physical injury. Ideally, epilepsy should be controlled with a single anti-epileptic drug before becoming pregnant. Regarding anti-epileptic drugs: - Levetiracetam, lamotrigine and carbamazepine are the safer anti-epileptic medication in pregnancy - Sodium valproate is avoided as it causes neural tube defects and developmental delay - Phenytoin is avoided as it causes cleft lip and palate There are a lot of warnings about the teratogenic effects of sodium valproate. It must be avoided in girls or women unless there are no suitable alternatives and strict criteria are met to ensure they do not get pregnant. There is a specific program for this, called Prevent (valproate pregnancy prevention programme).

Answer 112

Rheumatoid arthritis is an autoimmune condition that causes chronic inflammation of the synovial lining of the joints, tendon sheaths and bursa. It is an inflammatory arthritis. It is treated with disease-modifying anti-rheumatic drugs (DMARDs). Ideally, rheumatoid arthritis should be well controlled for at least three months before becoming pregnant. Often the symptoms of rheumatoid arthritis will improve during pregnancy, and may flare up after delivery. The treatment regime may need to be altered by a specialist rheumatologist before and during pregnancy: - Methotrexate is contraindicated, and is teratogenic, causing miscarriage and congenital abnormalities - Hydroxychloroquine is considered safe during pregnancy and is often the first-line choice - Sulfasalazine is considered safe during pregnancy - Corticosteroids may be used during flare-ups

Answer 113

1. Non-Steroidal Anti-Inflammatory Drugs They work by blocking prostaglandins. Prostaglandins are important in maintaining the ductus arteriosus in the fetus and neonate. Prostaglandins also soften the cervix and stimulate uterine contractions at the time of delivery. NSAIDS are generally avoided in pregnancy unless really necessary (e.g. in rheumatoid arthritis). They are particularly avoided in the third trimester, as they can cause premature closure of the ductus arteriosus in the fetus. They can also delay labour. 2. Beta-Blockers Labetalol is the most frequently used beta-blocker in pregnancy, and is first-line for high blood pressure caused by pre-eclampsia. Beta-blockers can cause: -Fetal growth restriction -Hypoglycaemia in the neonate -Bradycardia in the neonate 3. ACE Inhibitors and ARBs Medications that block the renin-angiotensin system (ACE inhibitors and ARBs) can cross the placenta and enter the fetus. In the fetus, they mainly affect the kidneys, and reduce the production of urine (and therefore amniotic fluid). The other notable effect is hypocalvaria, which is an incomplete formation of the skull bones. ACE inhibitors and ARBs, when used in pregnancy, can cause: -Oligohydramnios (reduced amniotic fluid) -Miscarriage or fetal death -Hypocalvaria (incomplete formation of the skull bones) -Renal failure in the neonate -Hypotension in the neonate 4. Opiates The use of opiates during pregnancy can cause withdrawal symptoms in the neonate after birth. This is called neonatal abstinence syndrome (NAS). NAS presents between 3 – 72 hours after birth with irritability, tachypnoea (fast breathing), high temperatures and poor feeding. 5. Warfarin Warfarin may be used in younger patients with recurrent venous thrombosis, atrial fibrillation or metallic mechanical heart valves. It crosses the placenta and is considered teratogenic in pregnancy, therefore it is avoided in pregnant women. Warfarin can cause: -Fetal loss -Congenital malformations, particularly craniofacial problems -Bleeding during pregnancy, postpartum haemorrhage, fetal haemorrhage and intracranial bleeding 6. Sodium Valproate The use of sodium valproate in pregnancy causes neural tube defects and developmental delay. 7. Lithium It is avoided in pregnant women or those planning pregnancy unless other options (i.e. antipsychotics) have failed. Lithium is particularly avoided in the first trimester, as this is linked with congenital cardiac abnormalities. In particular, it is associated with Ebstein’s anomaly, where the tricuspid valve is set lower on the right side of the heart (towards the apex), causing a bigger right atrium and a smaller right ventricle. When lithium is used, levels need to be monitored closely. Lithium also enters breast milk and is toxic to the infant, so should be avoided in breastfeeding. 8. Selective Serotonin Reuptake Inhibitors SSRIs can cross the placenta into the fetus. The risks need to be balanced against the benefits of treatment. The risks associated with untreated depression can be very significant. Women need to be aware of the potential risks of SSRIs in pregnancy: - First-trimester use has a link with congenital heart defects, First-trimester use of paroxetine has a stronger link with congenital malformations - Third-trimester use has a link with persistent pulmonary hypertension in the neonate Neonates can experience withdrawal symptoms, usually only mild and not requiring medical management 9. Isotretinoin (Roaccutane) Isotretinoin is a retinoid medication (relating to vitamin A) that is used to treat severe acne. Isotretinoin is highly teratogenic, causing miscarriage and congenital defects. Women need very reliable contraception before, during and for one month after taking isotretinoin.

Answer 114

Rubella is also known as German measles. Congenital rubella syndrome is caused by maternal infection with the rubella virus during the first 20 weeks of pregnancy. The risk is highest before ten weeks gestation. Women planning to become pregnant should ensure they have had the MMR vaccine. When in doubt, they can be tested for rubella immunity. If they do not have antibodies to rubella, they can be vaccinated with two doses of the MMR, three months apart. Pregnant women should not receive the MMR vaccination, as this is a live vaccine. Non-immune women should be offered the vaccine after giving birth. The features of congenital rubella syndrome to be aware of are: -Congenital deafness -Congenital cataracts -Congenital heart disease (PDA and pulmonary stenosis) -Learning disability

Answer 115

Chickenpox is caused by the varicella zoster virus (VZV). It is dangerous in pregnancy because it can lead to: - More severe cases in the mother, such as varicella pneumonitis, hepatitis or encephalitis - Fetal varicella syndrome - Severe neonatal varicella infection (if infected around delivery) Mothers that have previously had chickenpox are immune and safe. When in doubt, IgG levels for VZV can be tested. A positive IgG for VZV indicates immunity. Women that are not immune to varicella may be offered the varicella vaccine before or after pregnancy. Exposure to chickenpox in pregnancy: 1. When the pregnant woman has previously had chickenpox, they are safe 2. When they are not sure about their immunity, test the VZV IgG levels. If positive, they are safe. 3. When they are not immune, they can be treated with IV varicella immunoglobulins as prophylaxis against developing chickenpox. This should be given within ten days of exposure. When the chickenpox rash starts in pregnancy, they may be treated with oral aciclovir if they present within 24 hours and are more than 20 weeks gestation. Congenital varicella syndrome occurs in around 1% of cases of chickenpox in pregnancy. It occurs when infection occurs in the first 28 weeks of gestation. The typical features include: -Fetal growth restriction -Microcephaly, hydrocephalus and learning disability -Scars and significant skin changes located in specific dermatomes -Limb hypoplasia (underdeveloped limbs) -Cataracts and inflammation in the eye (chorioretinitis)

Answer 116

Listeria is an infectious gram-positive bacteria that causes listeriosis. Listeriosis is many times more likely in pregnant women compared with non-pregnant individuals. Infection in the mother may be asymptomatic, cause a flu-like illness, or less commonly cause pneumonia or meningoencephalitis. Listeriosis in pregnant women has a high rate of miscarriage or fetal death. It can also cause severe neonatal infection. Listeria is typically transmitted by unpasteurised dairy products, processed meats and contaminated foods. Pregnant women are advised to avoid high-risk foods (e.g. blue cheese) and practice good food hygiene.

Answer 117

Congenital cytomegalovirus infection occurs due to a cytomegalovirus (CMV) infection in the mother during pregnancy. The virus is mostly spread via the infected saliva or urine of asymptomatic children. Most cases of CMV in pregnancy do not cause congenital CMV. The features of congenital CMV are: -Fetal growth restriction -Microcephaly -Hearing loss -Vision loss -Learning disability -Seizures

Answer 118

Infection with the Toxoplasma gondii parasite is usually asymptomatic. It is primarily spread by contamination with faeces from a cat that is a host of the parasite. When infection occurs during pregnancy, it can lead to congenital toxoplasmosis. The risk is higher later in the pregnancy. There is a classic triad of features in congenital toxoplasmosis: -Intracranial calcification -Hydrocephalus -Chorioretinitis (inflammation of the choroid and retina in the eye)

Answer 119

Infections with parvovirus B19 in pregnancy can lead to several complications, particularly in the first and second trimesters. Complications are: -Miscarriage or fetal death -Severe fetal anaemia -Hydrops fetalis (fetal heart failure) -Maternal pre-eclampsia-like syndrome Fetal anaemia is caused by parvovirus infection of the erythroid progenitor cells in the fetal bone marrow and liver. These cells produce red blood cells, and the infection causes them to produce faulty red blood cells that have a shorter life span. Less red blood cells results in anaemia. This anaemia leads to heart failure, referred to as hydrops fetalis. Maternal pre-eclampsia-like syndrome is also known as mirror syndrome. It can be a rare complication of severe fetal heart failure (hydrops fetalis). It involves a triad of hydrops fetalis, placental oedema and oedema in the mother. It also features hypertension and proteinuria. Women suspected of parvovirus infection need tests for: - IgM to parvovirus, which tests for acute infection within the past four weeks - IgG to parvovirus, which tests for long term immunity to the virus after a previous infection - Rubella antibodies (as a differential diagnosis) Treatment is supportive. Women with parvovirus B19 infection need a referral to fetal medicine to monitor for complications and malformations.

Answer 120

Parvovirus B19 infection typically affects children. It is also known as fifth disease, slapped cheek syndrome and erythema infectiosum. It is caused by the parvovirus B19 virus. The illness is self-limiting, and the rash and symptoms usually fade over 1 – 2 weeks. Parvovirus infection starts with non-specific viral symptoms. After 2 – 5 days, the rash appears quite rapidly as a diffuse bright red rash on both cheeks, as though they have “slapped cheeks”. A few days later a reticular mildly erythematous rash affecting the trunk and limbs appears, which can be raised and itchy. Reticular means net-like. Healthy children and adults have a low risk of any complications, and management is supportive. They are infectious 7 – 10 days before the rash appears. They are not infectious once the rash has appeared. Significant exposure to parvovirus is classed as 15 minutes in the same room, or face-to-face contact, with someone that has the virus.

Answer 121

The zika virus is spread by host Aedes mosquitos in areas of the world where the virus is prevalent. It can also be spread by sex with someone infected with the virus. It can cause no symptoms, minimal symptoms, or a mild flu-like illness. In pregnancy, it can lead to congenital Zika syndrome, which involves: -Microcephaly -Fetal growth restriction -Other intracranial abnormalities, such as ventriculomegaly and cerebellar atrophy Pregnant women that may have contracted the Zika virus should be tested with viral PCR and antibodies to the Zika virus. Women with a positive result should be referred to fetal medicine for close monitoring of the pregnancy. There is no treatment for the virus.

Answer 122

The name rhesus refers to various types of rhesus antigens on the surface of red blood cells. The antigens on the red blood cells vary between individuals. The rhesus antigens are separate to the ABO blood group system. Within the rhesus group, many different types of antigens can be present or absent, depending on the person’s blood type. The most relevant antigen within the rhesus blood group system is the rhesus-D antigen. When we refer to someone’s rhesus status in relation to pregnancy (e.g. “she is rhesus-negative”), we are usually referring to whether they have the rhesus-D antigen present on their red blood cell surface.

Answer 123

Women that are rhesus-D positive do not need any additional treatment during pregnancy. When a woman that is rhesus-D negative becomes pregnant, we have to consider the possibility that her child will be rhesus positive. It is likely at some point in the pregnancy (i.e. childbirth) that the blood from the baby will find a way into the mother’s bloodstream. When this happens, the baby’s red blood cells display the rhesus-D antigen. The mother’s immune system will recognise this rhesus-D antigen as foreign, and produce antibodies to the rhesus-D antigen. The mother has then become sensitised to rhesus-D antigens. Usually, this sensitisation process does not cause problems during the first pregnancy. During subsequent pregnancies, the mother’s anti-rhesus-D antibodies can cross the placenta into the fetus. If that fetus is rhesus-D positive, these antibodies attach themselves to the red blood cells of the fetus and causes the immune system of the fetus to attack them, causing the destruction of the red blood cells (haemolysis). The red blood cell destruction caused by antibodies from the mother is called haemolytic disease of the newborn.

Answer 124

Prevention of sensitisation is the mainstay of management. This involves giving intramuscular anti-D injections to rhesus-D negative women. There is no way to reverse the sensitisation process once it has occurred, which is why prophylaxis is so essential. The anti-D medication works by attaching itself to the rhesus-D antigens on the fetal red blood cells in the mothers circulation, causing them to be destroyed. This prevents the mother’s immune system recognising the antigen and creating it’s own antibodies to the antigen. It acts as a prevention for the mother becoming sensitised to the rhesus-D antigen. Anti-D injections are given routinely on two occasions: -28 weeks gestation -Birth (if the baby’s blood group is found to be rhesus-positive) Anti-D injections should also be given at any time where sensitisation may occur, such as: -Antepartum haemorrhage -Amniocentesis procedures -Abdominal trauma Anti-D is given within 72 hours of a sensitisation event. After 20 weeks gestation, the Kleinhauer test is performed to see how much fetal blood has passed into the mother’s blood, to determine whether further doses of anti-D are required.

Answer 125

The Kleihauer test checks how much fetal blood has passed into the mother’s blood during a sensitisation event. This test is used after any sensitising event past 20 weeks gestation, to assess whether further doses of anti-D are required. The Kleihauer test involves adding acid to a sample of the mother’s blood. Fetal haemoglobin is naturally more resistant to acid, so that they are protected against the acidosis that occurs around childbirth. Therefore, fetal haemoglobin persists in response to the added acid, while the mothers haemoglobin is destroyed. The number of cells still containing haemoglobin (the remaining fetal cells) can then be calculated.

Answer 126

Small for gestational age is defined as a fetus that measures below the 10th centile for their gestational age. Two measurements on ultrasound are used to assess the fetal size: -Estimated fetal weight (EFW) -Fetal abdominal circumference (AC) Customised growth charts are used to assess the size of the fetus, based on the mother’s: - Ethnic group - Weight - Height -Parity Severe SGA is when the fetus is below the 3rd centile for their gestational age. Low birth weight is defined as a birth weight of less than 2500g.

Answer 127

The causes of SGA can be divided into two categories: 1. Constitutionally small, matching the mother and others in the family, and growing appropriately on the growth chart 2. Fetal growth restriction (FGR), also known as intrauterine growth restriction (IUGR) FGR/IUGR is when there is a small fetus (or a fetus that is not growing as expected) due to a pathology reducing the amount of nutrients and oxygen being delivered to the fetus through the placenta. The causes of fetal growth restriction can be divided into two categories: 1. Placenta mediated growth restriction 2. Non-placenta mediated growth restriction, where the baby is small due to a genetic or structural abnormality 1. Placenta mediated growth restriction refers to conditions that affect the transfer of nutrients across the placenta: -Idiopathic -Pre-eclampsia -Maternal smoking -Maternal alcohol -Anaemia -Malnutrition -Infection -Maternal health conditions 2. Non-placenta mediated growth restriction refers to pathology of the fetus, such as: -Genetic abnormalities -Structural abnormalities -Fetal infection -Errors of metabolism

Answer 128

There may be other signs that would indicate FGR other than the fetus being SGA, such as: -Reduced amniotic fluid volume -Abnormal Doppler studies -Reduced fetal movements -Abnormal CTGs

Answer 129

Short term complications of fetal growth restriction include: -Fetal death or stillbirth -Birth asphyxia -Neonatal hypothermia -Neonatal hypoglycaemia Growth restricted babies have a long term increased risk of: -Cardiovascular disease, particularly hypertension -Type 2 diabetes -Obesity -Mood and behavioural problems

Answer 130

There are a long list of risk factors for SGA: -Previous SGA baby -Obesity -Smoking -Diabetes -Existing hypertension -Pre-eclampsia -Older mother (over 35 years) -Multiple pregnancy -Low pregnancy‑associated plasma protein‑A (PAPPA) -Antepartum haemorrhage -Antiphospholipid syndrome

Answer 131

At the booking clinic, women are assessed for risk factors for SGA. Low-risk women have monitoring of the symphysis fundal height (SFH) at every antenatal appointment from 24 weeks onwards to identify potential SGA. The SFH is plotted on a customised growth chart to assess the appropriate size for the individual woman. If the symphysis fundal height is less than the 10th centile, women are booked for serial growth scans with umbilical artery doppler. Women are booked for serial growth scans with umbilical artery doppler if they have: -Three or more minor risk factors -One or more major risk factors -Issues with measuring the symphysis fundal height (e.g. large fibroids or BMI > 35) Women at risk or with SGA are monitored closely with serial ultrasound scans measuring: -Estimated fetal weight (EFW) and abdominal circumference (AC) to determine the growth velocity -Umbilical arterial pulsatility index (UA-PI) to measure flow through the umbilical artery -Amniotic fluid volume The local guidelines for the initiation and frequency of ultrasound scans may vary. An example regime is a growth scan every four weeks from 28 weeks gestation. Ultrasound frequency is increased where there is reduced growth velocity or problems with umbilical flow.

Answer 132

The critical management steps are: 1. Identifying those at risk of SGA 2. Aspirin is given to those at risk of pre-eclampsia 3. Treating modifiable risk factors (e.g. stop smoking) 4. Serial growth scans to monitor growth 5. Early delivery where growth is static, or there are other concerns When a fetus is identified as SGA, investigations to identify the underlying cause include: - Blood pressure and urine dipstick for pre-eclampsia - Uterine artery doppler scanning - Detailed fetal anatomy scan by fetal medicine - Karyotyping for chromosomal abnormalities - Testing for infections (e.g. toxoplasmosis, cytomegalovirus, syphilis and malaria) Early delivery is considered when growth is static on the growth charts, or other problems are identified (e.g. abnormal Doppler results). This reduces the risk of stillbirth. Corticosteroids are given when delivery is planned early, particularly when delivered by caesarean section. Paediatricians should be involved at birth to help with neonatal resuscitation and management if required.

Answer 133

Babies are defined as being large for gestational age (also known as macrosomia) when the weight of the newborn is more than 4.5kg at birth. During pregnancy, an estimated fetal weight above the 90th centile is considered large for gestational age.

Answer 134

-Constitutional -Maternal diabetes -Previous macrosomia -Maternal obesity or rapid weight gain -Overdue -Male baby

Answer 135

The risks to the mother include: -Shoulder dystocia -Failure to progress -Perineal tears -Instrumental delivery or caesarean -Postpartum haemorrhage -Uterine rupture (rare) The risks to the baby include: - Birth injury (Erbs palsy, clavicular fracture, fetal distress and hypoxia) - Neonatal hypoglycaemia - Obesity in childhood and later life - Type 2 diabetes in adulthood

Answer 136

Investigations for a large for gestational age baby are: - Ultrasound to exclude polyhydramnios and estimate the fetal weight - Oral glucose tolerance test for gestational diabetes Most women with large for gestational age pregnancy will have a successful vaginal delivery. Advise against induction of labour only on the grounds of macrosomia. The main risk with a large for gestational age baby is shoulder dystocia. The risks at delivery can be reduced by: -Delivery on a consultant lead unit -Delivery by an experienced midwife or obstetrician -Access to an obstetrician and theatre if required -Active management of the third stage (delivery of the placenta) -Early decision for caesarean section if required -Paediatrician attending the birth

Answer 137

There are some key definitions to become familiar with relating to twin and multiple pregnancy: - Monozygotic: identical twins (from a single zygote) - Dizygotic: non-identical (from two different zygotes) - Monoamniotic: single amniotic sac - Diamniotic: two separate amniotic sacs - Monochorionic: share a single placenta - Dichorionic: two separate placentas The best outcomes are with diamniotic, dichorionic twin pregnancies, as each fetus has their own nutrient supply.

Answer 138

Multiple pregnancy is usually diagnosed on the dating ultrasound scan. Ultrasound is also used to determine the: - Gestational age - Number of placentas (chorionicity) and amniotic sacs (amnionicity) - Risk of Down’s syndrome (as part of the combined test) When determining the type of twins using an ultrasound scan: - Dichorionic diamniotic twins have a membrane between the twins, with a lambda sign or twin peak sign - Monochorionic diamniotic twins have a membrane between the twins, with a T sign - Monochorionic monoamniotic twins have no membrane separating the twins The lambda sign, or twin peak sign, refers to a triangular appearance where the membrane between the twins meets the chorion, as the chorion blends partially into the membrane. This indicates a dichorionic twin pregnancy (separate placentas). The T sign refers to where the membrane between the twins abruptly meets the chorion, giving a T appearance. This indicates a monochorionic twin pregnancy (single placenta).

Answer 139

Risks to the mother: -Anaemia -Polyhydramnios -Hypertension -Malpresentation -Spontaneous preterm birth -Instrumental delivery or caesarean -Postpartum haemorrhage Risks to the fetuses and neonates: -Miscarriage -Stillbirth -Fetal growth restriction -Prematurity -Twin-twin transfusion syndrome -Twin anaemia polycythaemia sequence -Congenital abnormalities

Answer 140

Twin-twin transfusion syndrome occurs when the fetuses share a placenta. It is called feto-fetal transfusion syndrome in pregnancies with more than two fetuses. When there is a connection between the blood supplies of the two fetuses, one fetus (the recipient) may receive the majority of the blood from the placenta, while the other fetus (the donor) is starved of blood. The recipient gets the majority of the blood, and can become fluid overloaded, with heart failure and polyhydramnios. The donor has growth restriction, anaemia and oligohydramnios. There will be a discrepancy between the size of the fetuses. Women with twin-twin transfusion syndrome need to be referred to a tertiary specialist fetal medicine centre. In severe cases, laser treatment may be used to destroy the connection between the two blood supplies.

Answer 141

Twin anaemia polycythaemia sequence is similar to twin-twin transfusion syndrome, but less acute. One twin becomes anaemic whilst the other develops polycythaemia (raised haemoglobin).

Answer 142

A specialist multiple pregnancy obstetric team manages women with a multiple pregnancy. Women with multiple pregnancies require additional monitoring for anaemia, with a full blood count at: - Booking clinic - 20 weeks gestation - 28 weeks gestation Additional ultrasound scans are required in multiple pregnancy to monitor for fetal growth restriction, unequal growth and twin-twin transfusion syndrome: - 2 weekly scans from 16 weeks for monochorionic twins - 4 weekly scans from 20 weeks for dichorionic twins Planned birth is offered between: - 32 and 33 + 6 weeks for uncomplicated monochorionic monoamniotic twins - 36 and 36 + 6 weeks for uncomplicated monochorionic diamniotic twins - 37 and 37 + 6 weeks for uncomplicated dichorionic diamniotic twins - Before 35 + 6 weeks for triplets Waiting beyond these dates is associated with an increased risk of fetal death. The timing of birth when there are complications is assessed on an individual basis. Corticosteroids are given before delivery to help mature the lungs.

Answer 143

Monoamniotic twins require elective caesarean section at between 32 and 33 + 6 weeks. Diamniotic twins (aim to deliver between 37 and 37 + 6 weeks): -Vaginal delivery is possible when the first baby has a cephalic presentation (head first) - Caesarean section may be required for the second baby after successful birth of the first baby - Elective caesarean is advised when the presenting twin is not cephalic presentation

Answer 144

Urinary tract infections in pregnant women increase the risk of preterm delivery. They may also increase the risk of other adverse pregnancy outcomes, such as low birth weight and pre-eclampsia.

Answer 145

Asymptomatic bacteriuria refers to bacteria present in the urine, without symptoms of infection. Pregnant women with asymptomatic bacteriuria are at higher risk of developing lower urinary tract infections and pyelonephritis, and subsequently at risk of preterm birth. Pregnant women are tested for asymptomatic bacteriuria at booking and routinely throughout pregnancy. This involves sending a urine sample to the lab for microscopy, culture and sensitivities (MC&S). Testing for bacteria in the urine of asymptomatic patients is not recommended as it may lead to unnecessary antibiotics. Pregnant women are an exception to this rule, due to the adverse outcomes associated with infection.

Answer 146

1. Lower urinary tract infections present with: - Dysuria (pain, stinging or burning when passing urine) - Suprapubic pain or discomfort - Increased frequency of urination - Urgency - Incontinence - Haematuria 2. Pyelonephritis presents with: - Fever (more prominent than in lower urinary tract infections) - Loin, suprapubic or back pain (this may be bilateral or unilateral) - Looking and feeling generally unwell - Vomiting - Loss of appetite - Haematuria - Renal angle tenderness on examination

Answer 147

Nitrites are produced by gram-negative bacteria (such as E. coli). These bacteria break down nitrates, a normal waste product in urine, into nitrites. The nitrites in the urine suggest the presence of bacteria. Leukocytes refer to white blood cells. There are normally a small number of leukocytes in the urine, but a significant rise can be the result of an infection, or alternative cause of inflammation. Urine dipstick tests examine for leukocyte esterase, a product of leukocytes, which gives an indication to the number of leukocytes in the urine. Nitrites are a more accurate indication of infection than leukocytes. During pregnancy, midstream urine (MSU) samples are routinely sent to the microbiology lab to be cultured and to have sensitivity testing.

Answer 148

Most common cause of urinary tract infection is Escherichia coli (E. coli). This is a gram-negative, anaerobic, rod-shaped bacteria that is part of the normal lower intestinal microbiome. It is found in faeces, and can easily spread to the bladder. Other causes: - Klebsiella pneumoniae (gram-negative anaerobic rod) - Enterococcus - Pseudomonas aeruginosa - Staphylococcus saprophyticus - Candida albicans (fungal)

Answer 149

Urinary tract infection in pregnancy requires 7 days of antibiotics. The antibiotic options are: - Nitrofurantoin (avoid in the third trimester) - Amoxicillin (only after sensitivities are known) - Cefalexin Nitrofurantoin needs to be avoided in the third trimester as there is a risk of neonatal haemolysis (destruction of the neonatal red blood cells). Trimethoprim needs to be avoided in the first trimester as it is works as a folate antagonist. Folate is important in early pregnancy for the normal development of the fetus. Trimethoprim in early pregnancy can cause congenital malformations, particularly neural tube defects (i.e. spina bifida). It is not known to be harmful later in pregnancy, but is generally avoided unless necessary.

Answer 150

Anaemia is defined as a low concentration of haemoglobin in the blood. This is the result of an underlying disease and is not a disease itself. Haemoglobin is a protein found in red blood cells. It is responsible for picking up oxygen in the lungs and transporting it to the cells of the body. Iron is an essential ingredient in creating haemoglobin and forms part of the structure of the molecule. Women are routinely screened for anaemia twice during pregnancy: 1. Booking clinic 2. 28 weeks gestation During pregnancy, the plasma volume increases. This results in a reduction in the haemoglobin concentration. The blood is diluted due to the higher plasma volume. It is important to optimise the treatment of anaemia during pregnancy so that the woman has reasonable reserves, in case there is significant blood loss during delivery.

Answer 151

Often anaemia in pregnancy is asymptomatic. Women may have: - Shortness of breath - Fatigue - Dizziness - Pallor

Answer 152

The normal ranges for haemoglobin during pregnancy are: -Booking bloods: > 110 g/l -28 weeks gestation: > 105 g/l - Post partum: > 100 g/l The mean cell volume (MCV) can indicate the cause of the anaemia: - Low MCV may indicate iron deficiency - Normal MCV may indicate a physiological anaemia due to the increased plasma volume of pregnancy - Raised MCV may indicate B12 or folate deficiency Women are offered haemoglobinopathy screening at the booking clinic for thalassaemia (all women) and sickle cell disease (women at higher risk). Both are causes of significant anaemia in pregnancy. Additional investigations are not routinely performed, by may help establish the cause of the anaemia. They may include: -Ferritin -B12 -Folate

Answer 153

1. Iron Women with anaemia in pregnancy are started on iron replacement (e.g. ferrous sulphate 200mg three times daily). When women are not anaemic, but have a low ferritin (indicating low iron stores), they may be started on supplementary iron. 2. B12 The increased plasma volume and B12 requirements often result in a low B12 in pregnancy. Women with low B12 should be tested for pernicious anaemia (checking for intrinsic factor antibodies). Advice should be sought from a haematologist regarding further investigations and treatment of low B12 in pregnancy. Treatment options for low B12 are: - Intramuscular hydroxocobalamin injections - Oral cyanocobalamin tablets 3. Folate All women should already be taking folic acid 400mcg per day. Women with folate deficiency are started on folic acid 5mg daily. 4. Thalassaemia and Sickle Cell Anaemia Women with a haemoglobinopathy will be managed jointly with a specialist haematologist. They require high dose folic acid (5mg), close monitoring and transfusions when required.

Answer 154

Venous thromboembolism (VTE) is a common and potentially fatal condition. It involves blood clots (thrombosis) developing in the circulation. Thrombosis occurs as a result of stagnation of blood, and in hyper-coagulable states, such as pregnancy. When a thrombosis develops in the venous circulation, it is called deep vein thrombosis (DVT). This thrombosis can mobilise (embolisation) from the deep veins and travel to the lungs, where it becomes lodged in the pulmonary arteries. This blocks blood flow to related areas of the lungs, and is called a pulmonary embolism (PE). Pulmonary embolism is a significant cause of death in obstetrics. The risk is significantly reduced with VTE prophylaxis. The risk is highest in the postpartum period.

Answer 155

There is a long list of risk factors for VTE in pregnancy: -Smoking -Parity ≥ 3 -Age > 35 years -BMI > 30 -Reduced mobility -Multiple pregnancy -Pre-eclampsia -Gross varicose veins -Immobility -Family history of VTE -Thrombophilia -IVF pregnancy The RCOG advise starting prophylaxis from: - 28 weeks if there are three risk factors - First trimester if there are four or more of these risk factors There are additional scenarios where prophylaxis is considered, even in the absence of other risk factors: - Hospital admission - Surgical procedures - Previous VTE - Medical conditions such as cancer or arthritis - High-risk thrombophilias - Ovarian hyperstimulation syndrome

Answer 156

All pregnant women should have a risk assessment for their risk of venous thromboembolism (VTE) at booking. A risk assessment is performed again after birth. Additional risk assessments are necessary at other times, such as if they are admitted to hospital, undergo a procedure or develop significant immobility Each unit will have a policy and protocol for assessing risk and starting prophylaxis in pregnancy. Women at increased risk of VTE should receive prophylaxis with low molecular weight heparin (LMWH) unless contraindicated. Examples of LMWH are enoxaparin, dalteparin and tinzaparin. Prophylaxis is started as soon as possible in very high risk patients and at 28 weeks in those at high risk. It is continued throughout the antenatal period and for six weeks postnatally. Prophylaxis is temporarily stopped when the woman goes into labour, and can be started immediately after delivery (except with postpartum haemorrhage, spinal anaesthesia and epidurals). Mechanical prophylaxis may be considered in women with contraindications to LMWH. The options for mechanical prophylaxis are: -Intermittent pneumatic compression with equipment that inflates and deflates to massage the legs -Anti-embolic compression stockings

Answer 157

Deep vein thrombosis is almost always unilateral. Bilateral DVTs are rare, and bilateral symptoms are more likely due to an alternative diagnosis such as chronic venous insufficiency or heart failure. DVTs present with: -Calf or leg swelling -Dilated superficial veins -Tenderness to the calf (particularly over the deep veins) -Oedema -Colour changes to the leg To examine for leg swelling measure the circumference of the calf 10cm below the tibial tuberosity. More than 3cm difference between calves is significant.

Answer 158

Pulmonary embolism can present with subtle signs and symptoms. In patients with potential features of a PE, risk factors for PE, and no other explanation for their symptoms, have a low threshold for suspecting a PE. Presenting features include: -Shortness of breath -Cough with or without blood (haemoptysis) -Pleuritic chest pain -Hypoxia -Tachycardia (this can be difficult to distinguish from the normal physiological changes in pregnancy) -Raised respiratory rate -Low-grade fever -Haemodynamic instability causing hypotension

Answer 159

Doppler ultrasound is the investigation of choice for patients with suspected deep vein thrombosis. The RCOG recommends repeating negative ultrasound scans on day 3 and 7 in patients with a high index of suspicion for DVT. Women with suspected pulmonary embolism require: - Chest xray - ECG There are two main options for establishing a definitive diagnosis: CT pulmonary angiogram (CTPA) or ventilation-perfusion (VQ) scan. - CT pulmonary angiogram involves a chest CT scan with an intravenous contrast that highlights the pulmonary arteries to demonstrate any blood clots. This is usually the first choice for investigating a pulmonary embolism, as it tends to be more readily available, provides a more definitive assessment and gives information about alternative diagnoses such as pneumonia or malignancy. - Ventilation-perfusion (VQ) scan involves using radioactive isotopes and a gamma camera, to compare the ventilation with the perfusion of the lungs. First, the isotopes are inhaled to fill the lungs, and a picture is taken to demonstrate ventilation. Next, a contrast containing isotopes is injected, and a picture is taken to demonstrate perfusion. The two images are compared. With a pulmonary embolism, there will be a deficit in perfusion, as the thrombus blocks blood flow to the lung tissue. This area of lung tissue will be ventilated but not perfused. When considering the choice between CTPA and VQ scan: - CTPA is the test for choice for patients with an abnormal chest xray: CTPA carries a higher risk of breast cancer for the mother (minimal absolute risk) - VQ scan carriers a higher risk of childhood cancer for the fetus (minimal absolute risk) Patients with a suspected deep vein thrombosis and pulmonary embolism should have a Doppler ultrasound initially, and if a DVT is present, they do not require a VQ scan or CTPA to confirm a PE. The treatment for DVT and PE are the same. *The Wells score is not validated for use in pregnant women. D-dimers are not helpful in pregnant patients, as pregnancy is a cause of a raised D-dimer.*

Answer 160

Management of venous thromboembolism in pregnancy is with low molecular weight heparin (LMWH). Examples of LMWH are enoxaparin, dalteparin and tinzaparin. The dose is based on the woman’s weight at the booking clinic, or from early pregnancy. LMWH should be started immediately, before confirming the diagnosis in patients where DVT or PE is suspected and there is a delay in getting the scan. Treatment can be stopped when the investigations exclude the diagnosis. When the diagnosis is confirmed, LMWH is continued for the remained of pregnancy, plus six weeks postnatally, or three months in total (whichever is longer). There is an option to switch to oral anticoagulation (e.g. warfarin or a DOAC) after delivery. An individual risk assessment is performed before stopping anticoagulation, with advice from a haematologist if necessary. Women with a massive PE and haemodynamic compromise need immediate management by an experienced team of medical doctors, obstetricians, radiologists and others. This is a life-threatening scenario. Treatment options are: - Unfractionated heparin - Thrombolysis - Surgical embolectomy

Answer 161

Pre-eclampsia refers to new high blood pressure (hypertension) in pregnancy with end-organ dysfunction, notably with proteinuria (protein in the urine). It occurs after 20 weeks gestation, when the spiral arteries of the placenta form abnormally, leading to a high vascular resistance in these vessels. Pre-eclampsia is a significant cause of maternal and fetal morbidity and mortality. Without treatment, it can lead to maternal organ damage, fetal growth restriction, seizures, early labour and in a small proportion, death. Pre-eclampsia features a triad of: -Hypertension -Proteinuria -Oedema

Answer 162

- Chronic hypertension is high blood pressure that exists before 20 weeks gestation and is longstanding. This is not caused by dysfunction in the placenta and is not classed as pre-eclampsia. - Pregnancy-induced hypertension or gestational hypertension is hypertension occurring after 20 weeks gestation, without proteinuria. - Pre-eclampsia is pregnancy-induced hypertension associated with organ damage, notably proteinuria. - Eclampsia is when seizures occur as a result of pre-eclampsia.

Answer 163

The pathophysiology of pre-eclampsia is poorly understood. The following is a simplified explanation. When the blastocyst implants on the endometrium, the outermost layer, called the syncytiotrophoblast, grows into the endometrium. It forms finger-like projections called chorionic villi. The chorionic villi contain fetal blood vessels. Trophoblast invasion of the endometrium sends signals to the spiral arteries in that area of the endometrium, reducing their vascular resistance and making them more fragile. The blood flow to these arteries increases, and eventually they break down, leaving pools of blood called lacunae (lakes). Maternal blood flows from the uterine arteries, into these lacunae, and back out through the uterine veins. Lacunae form at around 20 weeks gestation. When the process of forming lacunae is inadequate, the woman can develop pre-eclampsia. Pre-eclampsia is caused by high vascular resistance in the spiral arteries and poor perfusion of the placenta. This causes oxidative stress in the placenta, and the release of inflammatory chemicals into the systemic circulation, leading to systemic inflammation and impaired endothelial function in the blood vessels.

Answer 164

High-risk factors are: -Pre-existing hypertension -Previous hypertension in pregnancy -Existing autoimmune conditions (e.g. systemic lupus erythematosus) -Diabetes -Chronic kidney disease Moderate-risk factors are: -Older than 40 -BMI > 35 -More than 10 years since previous pregnancy -Multiple pregnancy -First pregnancy -Family history of pre-eclampsia These risk factors are used to determine which women are offered aspirin as prophylaxis against pre-eclampsia. Women are offered aspirin from 12 weeks gestation until birth if they have one high-risk factor or more than one moderate-risk factors.

Answer 165

Pre-eclampsia has symptoms of the complications: -Headache -Visual disturbance or blurriness -Nausea and vomiting -Upper abdominal or epigastric pain (this is due to liver swelling) -Oedema -Reduced urine output -Brisk reflexes

Answer 166

Diagnosis can be made with a: -Systolic blood pressure above 140 mmHg -Diastolic blood pressure above 90 mmHg PLUS any of: -Proteinuria (1+ or more on urine dipstick) -Organ dysfunction (e.g. raised creatinine, elevated liver enzymes, seizures, thrombocytopenia or haemolytic anaemia) -Placental dysfunction (e.g. fetal growth restriction or abnormal Doppler studies) Proteinuria can be quantified using: - Urine protein:creatinine ratio (above 30mg/mmol is significant) - Urine albumin:creatinine ratio (above 8mg/mmol is significant) The NICE guidelines (2019) recommend the use of placental growth factor (PlGF) testing on one occasion during pregnancy in women suspected of having pre-eclampsia. Placental growth factor is a protein released by the placenta that functions to stimulate the development of new blood vessels. In pre-eclampsia, the levels of PlGF are low. NICE recommends using PlGF between 20 and 35 weeks gestation to rule-out pre-eclampsia.

Answer 167

All pregnant women are routinely monitored at every antenatal appointment for evidence of pre-eclampsia, with: -Blood pressure -Symptoms -Urine dipstick for proteinuria

Answer 168

When gestational hypertension (without proteinuria) is identified, the general management involves: - Treating to aim for a blood pressure below 135/85 mmHg -Admission for women with a blood pressure above 160/110 mmHg -Urine dipstick testing at least weekly -Monitoring of blood tests weekly (full blood count, liver enzymes and renal profile) -Monitoring fetal growth by serial growth scans -PlGF testing on one occasion

Answer 169

When pre-eclampsia is diagnosed, the general management is similar to gestational hypertension, except: -Scoring systems are used to determine whether to admit the woman (fullPIERS or PREP‑S) -Blood pressure is monitored closely (at least every 48 hours) -Urine dipstick testing is not routinely necessary (the diagnosis is already made) -Ultrasound monitoring of the fetus, amniotic fluid and dopplers is performed two weekly Medical management of pre-eclampsia is with: 1. Labetolol is first-line as an antihypertensive 2. Nifedipine (modified-release) is commonly used second-line 3. Methyldopa is used third-line (needs to be stopped within two days of birth) 4. Intravenous hydralazine may be used as an antihypertensive in critical care in severe pre-eclampsia or eclampsia 5. IV magnesium sulphate is given during labour and in the 24 hours afterwards to prevent seizures 6. Fluid restriction is used during labour in severe pre-eclampsia or eclampsia, to avoid fluid overload Planned early birth may be necessary if the blood pressure cannot be controlled or complications occur. Corticosteroids should be given to women having a premature birth to help mature the fetal lungs. Blood pressure is monitored closely after delivery. Blood pressure will return to normal over time once the placenta is removed. For medical treatment, NICE recommend after delivery switching to one or a combination of: -Enalapril (first-line) -Nifedipine or amlodipine (first-line in black African or Caribbean patients) -Labetolol or atenolol (third-line)

Answer 170

Eclampsia refers to the seizures associated with pre-eclampsia. IV magnesium sulphate is used to manage seizures associated with pre-eclampsia.

Answer 171

HELLP syndrome is a combination of features that occurs as a complication of pre-eclampsia and eclampsia. It is an acronym for the key characteristics: -Haemolysis -Elevated Liver enzymes -Low Platelets

Answer 172

Gestational diabetes refers to diabetes triggered by pregnancy. It is caused by reduced insulin sensitivity during pregnancy, and resolves after birth. The most significant immediate complication of gestational diabetes is a large for dates fetus and macrosomia. This has implications for birth, mainly posing a risk of shoulder dystocia. Longer-term, women are at higher risk of developing type 2 diabetes after pregnancy. Anyone with risk factors should be screened with an oral glucose tolerance test at 24 – 28 weeks gestation. Women with previous gestational diabetes also have an OGTT soon after the booking clinic.

Answer 173

- Previous gestational diabetes - Previous macrosomic baby (≥ 4.5kg) - BMI > 30 - Ethnic origin (black Caribbean, Middle Eastern and South Asian) - Family history of diabetes (first-degree relative)

Answer 174

The screening test of choice for gestational diabetes is an oral glucose tolerance test (OGTT). An OGTT is used in patients with risk factors for gestational diabetes, and also when there are features that suggest gestational diabetes: -Large for dates fetus -Polyhydramnios (increased amniotic fluid) -Glucose on urine dipstick An OGTT should be performed in the morning after a fast (they can drink plain water). The patient drinks a 75g glucose drink at the start of the test. The blood sugar level is measured before the sugar drink (fasting) and then at 2 hours. Normal results are: -Fasting: < 5.6 mmol/l -At 2 hours: < 7.8 mmol/l Results higher than these values are used to diagnose gestational diabetes. *It is really easy to remember the cutoff for gestational diabetes as simply 5 – 6 – 7 – 8.*

Answer 175

Patients with gestational diabetes are managed in joint diabetes and antenatal clinics, with input from a dietician. Women need careful explanation about the condition, and to learn how to monitor and track their blood sugar levels. They need four weekly ultrasound scans to monitor the fetal growth and amniotic fluid volume from 28 to 36 weeks gestation. 1. Fasting glucose less than 7 mmol/l: trial of diet and exercise for 1-2 weeks, followed by metformin, then insulin 2. Fasting glucose above 7 mmol/l: start insulin ± metformin 3. Fasting glucose above 6 mmol/l plus macrosomia (or other complications): start insulin ± metformin Glibenclamide (a sulfonylurea) is suggested as an option for women who decline insulin or cannot tolerate metformin. Women need to monitor their blood sugar levels several times a day. Target levels are: - Fasting: 5.3 mmol/l - 1 hour post-meal: 7.8 mmol/l - 2 hours post-meal: 6.4 mmol/l Avoiding levels of 4 mmol/l or below

Answer 176

Before becoming pregnant, women with existing diabetes should aim for good glucose control. They should take 5mg folic acid from preconception until 12 weeks gestation. Women with existing type 1 and type 2 diabetes should aim for the same target insulin levels as with gestational diabetes. Women with type 2 diabetes are managed using metformin and insulin, and other oral diabetic medications should be stopped. Retinopathy screening should be performed shortly after booking and at 28 weeks gestation. This involves referral to an ophthalmologist to check for diabetic retinopathy. Diabetes carries a risk of rapid progression of retinopathy, and interventions may be required. NICE advise a planned delivery between 37 and 38 + 6 weeks for women with pre-existing diabetes. (Women with gestational diabetes can give birth up to 40 + 6). A sliding-scale insulin regime is considered during labour for women with type 1 diabetes. A dextrose and insulin infusion is titrated to blood sugar levels, according to the local protocol. This is also considered for women with poorly controlled blood sugars with gestational or type 2 diabetes. *It is worth remembering the importance of retinopathy screening during pregnancy for women with existing diabetes.*

Answer 177

Diabetes improves immediately after birth. Women with gestational diabetes can stop their diabetic medications immediately after birth. They need follow up to test their fasting glucose after at least six weeks. Women with existing diabetes should lower their insulin doses and be wary of hypoglycaemia in the postnatal period. The insulin sensitivity will increase after birth and with breastfeeding. Babies of mothers with diabetes are at risk of: - Neonatal hypoglycaemia - Polycythaemia (raised haemoglobin) - Jaundice (raised bilirubin) - Congenital heart disease - Cardiomyopathy Babies need close monitoring for neonatal hypoglycaemia, with regular blood glucose checks and frequent feeds. The aim is to maintain their blood sugar above 2 mmol/l, and if it falls below this, they may need IV dextrose of nasogastric feeding. *If you remember two complications of gestational diabetes, remember macrosomia and neonatal hypoglycaemia. Babies become accustomed to a large supply of glucose during the pregnancy, and after birth they struggle to maintain the supply they are used to with oral feeding alone.*

Answer 178

Obstetric cholestasis is also known as intrahepatic cholestasis of pregnancy. Obstetric cholestasis is characterised by the reduced outflow of bile acids from the liver. The condition resolves after delivery of the baby. Obstetric cholestasis is a relatively common complication of pregnancy, occurring in around 1% of pregnant women. It usually develops later in pregnancy (i.e. after 28 weeks), and is thought to be the result of increased oestrogen and progesterone levels. There seems to be a genetic component. It is more common in women of South Asian ethnicity. Bile acids are produced in the liver from the breakdown of cholesterol. Bile acids flow from liver to the hepatic ducts, past the gallbladder and out of the bile duct to the intestines. In obstetric cholestasis, the outflow of bile acids is reduced, causing them to build up in the blood, resulting in the classic symptoms of itching (pruritis). Obstetric cholestasis is associated with an increased risk of stillbirth.

Answer 179

Obstetric cholestasis typically present later in pregnancy, particularly in the third trimester. Itching (pruritis) is the main symptom, particularly affecting the palms of the hands and soles of the feet. Other symptoms are related to cholestasis and outflow obstruction in the bile ducts: -Fatigue -Dark urine -Pale, greasy stools -Jaundice Importantly, there is no rash associated with obstetric cholestasis. If a rash is present, an alternative diagnosis should be considered, such as polymorphic eruption of pregnancy or pemphigoid gestationis.

Answer 180

- Gallstones - Acute fatty liver - Autoimmune hepatitis - Viral hepatitis

Answer 181

Women presenting with pruritus should have liver function tests and bile acids checked. Obstetric cholestasis will cause: - Abnormal liver function tests (LFTs), mainly ALT, AST and GGT - Raised bile acids *It is normal for alkaline phosphatase (ALP) to increase in pregnancy. This is because the placenta produces ALP. A rise in ALP without other abnormal LFT results is usually due to placental production of ALP, rather than liver pathology.*

Answer 182

Ursodeoxycholic acid is the primary treatment for obstetric cholestasis. It improves LFTs, bile acids and symptoms. Symptoms of itching can be managed with: - Emollients (i.e. calamine lotion) to soothe the skin - Antihistamines (e.g. chlorphenamine) can help sleeping (but does not improve itching) Water-soluble vitamin K can be given if clotting (prothrombin time) is deranged. Vitamin K is a fat-soluble vitamin. Bile acids are important in the absorption of fat-soluble vitamins in the intestines. A lack of bile acids can lead to vitamin K deficiency. Vitamin K is an important part of the clotting system, and deficiency can lead to impaired clotting of blood. Monitoring of LFTs is required during pregnancy (weekly) and after delivery (after at least ten days), to ensure the condition does not worsen and resolves after birth. Planned delivery after 37 weeks may be considered, particularly when the LFTs and bile acids are severely deranged. Stillbirth in obstetric cholestasis is difficult to predict, and early delivery aims to reduce the risk.

Answer 183

Acute fatty liver of pregnancy is a rare condition that occurs in the third trimester of pregnancy. There is a rapid accumulation of fat within the liver cells (hepatocytes), causing acute hepatitis. There is a high risk of liver failure and mortality, for both the mother and fetus.

Answer 184

Acute fatty liver of pregnancy results from impaired processing of fatty acids in the placenta. This is the result of a genetic condition in the fetus that impairs fatty acid metabolism. The most common cause is long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency in the fetus, which is an autosomal recessive condition. This mode of inheritance means the mother will also have one defective copy of the gene. Th LCHAD enzyme is important in fatty acid oxidation, breaking down fatty acids to be used as fuel. The fetus and placenta are unable to break down fatty acids. These fatty acids enter the maternal circulation, and accumulate in the liver. The mother’s defective copy of the gene may also contribute to the accumulation of fatty acids. The accumulation of fatty acids in the mother’s liver leads to inflammation and liver failure.

Answer 185

The presentation is with vague symptoms associated with hepatitis : -General malaise and fatigue -Nausea and vomiting -Jaundice -Abdominal pain -Anorexia (lack of appetite) -Ascites

Answer 186

Liver function tests will show elevated liver enzymes (ALT and AST). Other bloods may be deranged, with: -Raised bilirubin -Raised WBC count -Deranged clotting (raised prothrombin time and INR) -Low platelets *In your exams, elevated liver enzymes and low platelets should make you think of HELLP syndrome rather than acute fatty liver of pregnancy. HELLP syndrome is much more common, but keep acute fatty liver of pregnancy in mind as a differential*

Answer 187

Acute fatty liver of pregnancy is an obstetric emergency and requires prompt admission and delivery of the baby. Most patients will recover after delivery. Management also involves treatment of acute liver failure if it occurs, including consideration of liver transplant.

Answer 188

Polymorphic eruption of pregnancy is also known as pruritic and urticarial papules and plaques of pregnancy. It is an itchy rash that tends to start in the third trimester. It usually begins on the abdomen, particularly associated with stretch marks (striae). It is characterised by: -Urticarial papules (raised itchy lumps) -Wheals (raised itchy areas of skin) -Plaques (larger inflamed areas of skin) The condition will get better towards the end of pregnancy and after delivery. Management is to control the symptoms, with: -Topical emollients -Topical steroids -Oral antihistamines -Oral steroids may be used in severe cases

Answer 189

Atopic eruption of pregnancy essentially refers to eczema that flares up during pregnancy. This includes both women that have never suffered with eczema and those with pre-existing eczema. Atopic eruption of pregnancy presents in the first and second trimester of pregnancy. There are two types: - E-type, or eczema-type: with eczematous, inflamed, red and itchy skin, typically affecting the insides of the elbows, back of knees, neck, face and chest. - P-type, or prurigo-type: with intensely itchy papules (spots) typically affecting the abdomen, back and limbs. The condition will usually get better after delivery. Management is with: -Topical emollients -Topical steroids -Phototherapy with ultraviolet light (UVB) may be used in severe cases -Oral steroids may be used in severe cases

Answer 190

Melasma is also known as mask of pregnancy. It is characterised by increased pigmentation to patches of the skin on the face. This is usually symmetrical and flat, affecting sun-exposed areas. Melasma is thought to be partly related to the increased female sex hormones associated with pregnancy. It can also occur with the combined contraceptive pill and hormone replacement therapy. It is also associated with sun exposure, thyroid disease and family history. No active treatment is required if the appearance is acceptable to the woman. Management is with: -Avoiding sun exposure and using suncream -Makeup (camouflage) -Skin lightening cream (e.g. hydroquinone or retinoid creams), although not in pregnancy and only under specialist care -Procedures such as chemical peels or laser treatment (not usually on the NHS)

Answer 191

Pyogenic granuloma is also known as lobular capillary haemangioma. This is a benign, rapidly growing tumour of capillaries. It present as a discrete lump with a red or dark appearance. They occur more often in pregnancy, and can also be associated with hormonal contraceptives. They can also be triggered by minor trauma or infection. Pyogenic granuloma present with a rapidly growing lump that develops over days up to 1-2 cm in size, (but can be larger). They often occur on fingers, or on the upper chest, back, neck or head. They may cause profuse bleeding and ulceration if injured. Other differentials, such as malignancy, need to be excluded (particularly nodular melanoma). When they occur in pregnancy, they usually resolve without treatment after delivery. Treatment is with surgical removal with histology to confirm the diagnosis.

Answer 192

Pemphigoid gestationis is a rare autoimmune skin condition that occurs in pregnancy. Autoantibodies are created that damage the connection between the epidermis and the dermis. The pregnant woman’s immune system may produce these antibodies in response to placental tissue. This causes the epidermis and dermis to separate, creating a space that can fill with fluid, resulting in large fluid-filled blisters (bullae). Pemphigoid gestationis usually occurs in the second or third trimester. The typical presentation is initially with an itchy red papular or blistering rash around the umbilicus, that then spreads to other parts of the body. Over several weeks, large fluid-filled blisters form. The rash usually resolves without treatment after delivery. It may go through stages of improvement and worsening during pregnancy and after birth. The blisters heal without scarring. Treatment is with: -Topical emollients -Topical steroids -Oral steroids may be required in severe cases -Immunosuppressants may be required where steroids are inadequate -Antibiotics may be necessary if infection occurs The risks to the baby are: -Fetal growth restriction -Preterm delivery -Blistering rash after delivery (as the maternal antibodies pass to the baby)

Answer 193

Placenta praevia is where the placenta is attached in the lower portion of the uterus, lower than the presenting part of the fetus. Praevia directly translates from Latin as “going before”. - Low-lying placenta is used when the placenta is within 20mm of the internal cervical os - Placenta praevia is used only when the placenta is over the internal cervical os Placenta praevia occurs in around 1% of pregnancies. It is a notable cause of antepartum haemorrhage. (The three causes of antepartum haemorrhage to remember are placenta praevia, placental abruption and vasa praevia. These are serious causes with high morbidity and mortality. Causes of spotting or minor bleeding in pregnancy include cervical ectropion, infection and vaginal abrasions from intercourse or procedures.)

Answer 194

Placenta praevia is associated with increased morbidity and mortality for the mother and fetus. The risks include: - Antepartum haemorrhage - Emergency caesarean section - Emergency hysterectomy - Maternal anaemia and transfusions - Preterm birth and low birth weight - Stillbirth

Answer 195

Traditionally, there are four grades of placenta praevia. You may still come across these in textbooks and exams: 1. Minor praevia, or grade I – the placenta is in the lower uterus but not reaching the internal cervical os 2. Marginal praevia, or grade II – the placenta is reaching, but not covering, the internal cervical os 3. Partial praevia, or grade III – the placenta is partially covering the internal cervical os 4. Complete praevia, or grade IV – the placenta is completely covering the internal cervical os The RCOG guidelines (2018) recommend against using this grading system, as it is considered outdated. The two descriptions used are low-lying placenta and placenta praevia.

Answer 196

The risk factors for placenta praevia are: - Previous caesarean sections - Previous placenta praevia - Older maternal age - Maternal smoking - Structural uterine abnormalities (e.g. fibroids) - Assisted reproduction (e.g. IVF)

Answer 197

The 20-week anomaly scan is used to assess the position of the placenta and diagnose placenta praevia. Many women with placenta praevia are asymptomatic. It may present with painless vaginal bleeding in pregnancy (antepartum haemorrhage). Bleeding usually occurs later in pregnancy (around or after 36 weeks).

Answer 198

For women with a low-lying placenta or placenta praevia diagnosed early in pregnancy (e.g. at the 20-week anomaly scan), s a repeat transvaginal ultrasound scan at: -32 weeks gestation -36 weeks gestation (if present on the 32-week scan, to guide decisions about delivery) Corticosteroids are given between 34 and 35 + 6 weeks gestation to mature the fetal lungs, given the risk of preterm delivery. Planned delivery is considered between 36 and 37 weeks gestation. It is planned early to reduce the risk of spontaneous labour and bleeding. Planned caesarean section is required with placenta praevia and low-lying placenta (<20mm from the internal os). Depending on the position of the placenta and fetus, different incisions may be made in the skin and uterus, for example, vertical incisions. Ultrasound may be around the time of the procedure to locate the placenta. Emergency caesarean section may be required with premature labour or antenatal bleeding. The main complication of placenta praevia is haemorrhage before, during and after delivery. When this occurs, urgent management is required and may involve: -Emergency caesarean section -Blood transfusions -Intrauterine balloon tamponade -Uterine artery occlusion -Emergency hysterectomy

Answer 199

Vasa praevia is a condition where the fetal vessels are within the fetal membranes (chorioamniotic membranes) and travel across the internal cervical os. The fetal membranes surround the amniotic cavity and developing fetus. The fetal vessels consist of the two umbilical arteries and single umbilical vein. Vasa praevia is where the vessels are placed over internal cervical os, before the fetus.

Answer 200

Under normal circumstances, the umbilical cord containing the fetal vessels (umbilical arteries and vein) inserts directly into the placenta. The fetal vessels are always protected, either by the umbilical cord or by the placenta. The umbilical cord contains Wharton’s jelly. Wharton’s jelly is a layer of soft connective tissue that surrounds the blood vessels in the umbilical cord, offering protection. There are two instances when the fetal vessels can be exposed, outside the protection of the umbilical cord or placenta: 1. Velamentous umbilical cord is where the umbilical cord inserts into the chorioamniotic membranes, and the fetal vessels travel unprotected through the membranes before joining the placenta. 2. An accessory lobe of the placenta (also known as a succenturiate lobe) is connected by fetal vessels that travel through the chorioamniotic membranes between the placental lobes. In vasa praevia, the fetal vessels are exposed, outside the protection of the umbilical cord or the placenta. The fetal vessels travel through the chorioamniotic membranes, and pass across the internal cervical os (the inner opening of the cervix). These exposed vessels are prone to bleeding, particularly when the membranes are ruptured during labour and at birth. This can lead to dramatic fetal blood loss and death. There are two types of vasa praevia: 1. Type I vasa praevia – the fetal vessels are exposed as a velamentous umbilical cord 2. Type II vasa praevia – the fetal vessels are exposed as they travel to an accessory placental lobe

Answer 201

- Low lying placenta - IVF pregnancy - Multiple pregnancy

Answer 202

Vasa praevia may be diagnosed by ultrasound during pregnancy. This is the ideal scenario, as it allows a planned caesarean section to reduce the risk of haemorrhage. However, ultrasound is not reliable, and it is often not possible to diagnose antenatally. It may present with antepartum haemorrhage, with bleeding during the second or third trimester of pregnancy. It may be detected by vaginal examination during labour, when pulsating fetal vessels are seen in the membranes through the dilated cervix. Finally, it may be detected during labour when fetal distress and dark-red bleeding occur following rupture of the membranes. This carries a very high fetal mortality, even with emergency caesarean section.

Answer 203

For asymptomatic women with vasa praevia: - Corticosteroids, given from 32 weeks gestation to mature the fetal lungs - Elective caesarean section, planned for 34 – 36 weeks gestation Where antepartum haemorrhage occurs, emergency caesarean section is required to deliver the fetus before death occurs. After stillbirth or unexplained fetal compromise during delivery, the placenta is examined for evidence of vasa praevia as a possible cause.

Answer 204

Placental abruption refers to when the placenta separates from the wall of the uterus during pregnancy. The site of attachment can bleed extensively after the placenta separates. Placental abruption is a significant cause of antepartum haemorrhage.

Answer 205

The risk factors for placental abruption are: -Previous placental abruption -Pre-eclampsia -Bleeding early in pregnancy -Trauma (consider domestic violence) -Multiple pregnancy -Fetal growth restriction -Multigravida -Increased maternal age -Smoking -Cocaine or amphetamine use

Answer 206

The typical presentation of placental abruption is with: - Sudden onset severe abdominal pain that is continuous - Vaginal bleeding (antepartum haemorrhage) - Shock (hypotension and tachycardia) - Abnormalities on the CTG indicating fetal distress - Characteristic “woody” abdomen on palpation, suggesting a large haemorrhage

Answer 207

1. Spotting: spots of blood noticed on underwear 2. Minor haemorrhage: less than 50ml blood loss 3. Major haemorrhage: 50 – 1000ml blood loss 4. Massive haemorrhage: more than 1000 ml blood loss, or signs of shock

Answer 208

Concealed abruption is where the cervical os remains closed, and any bleeding that occurs remains within the uterine cavity. The severity of bleeding can be significantly underestimated with concealed haemorrhage. Concealed abruption is opposed to revealed abruption, where the blood loss is observed via the vagina.

Answer 209

There are no reliable tests for diagnosing placental abruption. It is a clinical diagnosis based on the presentation. Placental abruption is an obstetric emergency. The urgency depends on the amount of placental separation, extent of bleeding, haemodynamic stability of the mother and condition of the fetus. It is important to consider concealed haemorrhage, where the vaginal bleeding may be disproportionate to the uterine bleeding. The initial steps with major or massive haemorrhage are: 1. Urgent involvement of a senior obstetrician, midwife and anaesthetist 2. 2 x grey cannula 3. Bloods include FBC, UE, LFT and coagulation studies 4. Crossmatch 4 units of blood 5. Fluid and blood resuscitation as required 6. CTG monitoring of the fetus 7. Close monitoring of the mother Ultrasound can be useful in excluding placenta praevia as a cause for antepartum haemorrhage, but is not very good at diagnosing or assessing abruption. Antenatal steroids are offered between 24 and 34 + 6 weeks gestation to mature the fetal lungs in anticipation of preterm delivery. Rhesus-D negative women require anti-D prophylaxis when bleeding occurs. A Kleihauer test is used to quantify how much fetal blood is mixed with the maternal blood, to determine the dose of anti-D that is required. Emergency caesarean section may be required where the mother is unstable, or there is fetal distress. There is an increased risk of postpartum haemorrhage after delivery in women with placental abruption. Active management of the third stage is recommended.

Answer 210

Placenta accreta refers to when the placenta implants deeper, through and past the endometrium, making it difficult to separate the placenta after delivery of the baby. It is referred to as placenta accreta spectrum, as there is a spectrum of severity in how deep and broad the abnormal implantation extends.

Answer 211

There are three layers to the uterine wall: 1. Endometrium, the inner layer that contains connective tissue (stroma), epithelial cells and blood vessels 2. Myometrium, the middle layer that contains smooth muscle 3. Perimetrium, the outer layer, which is a serous membrane similar to the peritoneum (also known as serosa) Usually the placenta attaches to the endometrium. This allows the placenta to separate cleanly during the third stage of labour, after delivery of the baby. With placenta accreta, the placenta embeds past the endometrium, into the myometrium and beyond. This may happen due to a defect in the endometrium. Imperfections may occur due to previous uterine surgery, such as a caesarean section or curettage procedure. The deep implantation makes it very difficult for the placenta to separate during delivery, leading to extensive bleeding (postpartum haemorrhage). There are three further definitions, depending on the depth of the insertion: 1. Superficial placenta accreta is where the placenta implants in the surface of the myometrium, but not beyond 2. Placenta increta is where the placenta attaches deeply into the myometrium 3. Placenta percreta is where the placenta invades past the myometrium and perimetrium, potentially reaching other organs such as the bladder

Answer 212

Placenta accreta does not typically cause any symptoms during pregnancy. It can present with bleeding (antepartum haemorrhage) in the third trimester. It may be diagnosed on antenatal ultrasound scans, and particular attention is given to women with a previous placenta accreta or caesarean during scanning. It may be diagnosed at birth, when it becomes difficult to deliver the placenta. It is a cause of significant postpartum haemorrhage.