Pregnancy, labour and delivery Flashcards
What are the key contraceptive methods available?
The key contraceptive methods available are:
-Natural family planning (“rhythm method”)
-Barrier methods (i.e. condoms)
-Combined contraceptive pills
-Progestogen-only pills
-Coils (i.e. copper coil or Mirena)
-Progestogen injection
-Progestogen implant
-Surgery (i.e. sterilisation or vasectomy)
Emergency contraception is also available after unprotected intercourse. However, emergency contraception should not be relied upon as a regular method of contraception.
What are the levels of UK Medical Eligibility Criteria (UKMEC) risk?
UKMEC 1: No restriction in use (minimal risk)
UKMEC 2: Benefits generally outweigh the risks
UKMEC 3: Risks generally outweigh the benefits
UKMEC 4: Unacceptable risk (typically this means the method is contraindicated)
What does ‘effectiveness’ describe for contraceptive methods?
The different methods of contraception are not equally effective. The effectiveness is expressed as a percentage. For example, the combined oral contraceptive is 99% effective. The only method that is 100% effective is complete abstinence.
What 99% effective means is that if an average person used this method of contraception correctly with a regular partner for a single year, they would only have a 1% chance of pregnancy.
It is essential to distinguish between the effectiveness of perfect use and typical use. This is especially important with methods such as natural family planning, barrier contraception and the pill, where the effectiveness is very user-dependent. Long-acting methods such as the implant, coil and surgery are the most effective with typical use, as they are not dependent on the user to take regular action.
What are the effectiveness percentages for perfect use and typical use of natural family planning and condoms?
Natural Family Planning
Perfect = 95 – 99.6%
Typical = 76%
Condoms
Perfect = 98%
Typical = 82%
Which contraceptive methods are >99% effective when used perfectly and what is their typical use effectiveness?
- Combined oral contraceptive pill
Typical use = 91% - Progestogen-only pill
Typical use = 91% - Progestogen-only injection
Typical use = 94% - Progestogen-only implant
- Coils (i.e. copper coil or Mirena)
- Surgery (i.e. sterilisation or vasectomy)
The typical use for these methods are not user-dependent so effectiveness is still >99%
What are the 3 key risk factors when choosing contraceptive methods and which methods are contraindicated?
- Breast cancer: avoid any hormonal contraception and go for the copper coil or barrier methods
- Cervical or endometrial cancer: avoid the intrauterine system (i.e. Mirena coil)
- Wilson’s disease: avoid the copper coil
Which risk factors contraindicate use of the combined contraceptive pill (UKMEC 4)?
-Uncontrolled hypertension (particularly ≥160 / ≥100)
-Migraine with aura
-History of VTE
-Aged over 35 smoking more than 15 cigarettes per day
-Major surgery with prolonged immobility
-Vascular disease or stroke
-Ischaemic heart disease, cardiomyopathy or atrial fibrillation
-Liver cirrhosis and liver tumours
-Systemic lupus erythematosus and antiphospholipid syndrome
What additional considerations are needed when prescribing contraception for older and perimenopausal women?
There are some additional considerations in older and perimenopausal women:
-After the last period, contraception is required for 2 years in women under 50 and 1 year in women over 50
-Hormone replacement therapy does not prevent pregnancy, and added contraception is required
-The combined contraceptive pill can be used up to age 50 years, and can treat perimenopausal symptoms
-The progestogen injection (i.e. Depo-Provera) should be stopped before 50 years due to the risk of osteoporosis
Women that are amenorrhoeic (no periods) when taking progestogen-only contraception should continue until either:
-FSH blood test results are above 30 IU/L on two tests taken six weeks apart (continue contraception for 1 more year)
- 55 years of age
What considerations are needed when prescribing contraception to women under 20 years old?
When prescribing contraception to women under 20 years:
-Combined and progestogen-only pills are unaffected by younger age
-The progestogen-only implant is a good choice of long-acting reversible contraception (UK MEC 1)
-The progestogen-only injection is UK MEC 2 due to concerns about reduced bone mineral density
-Coils are UKMEC 2, as they may have a higher rate of expulsion
What considerations are needed when prescribing contraception to women after childbirth?
Fertility is not considered to return until 21 days after giving birth, and contraception is not required up to this point. The risk of pregnancy is very low before 21 days. After 21 days women are considered fertile, and will need contraception (including condoms for 7 days when starting the combined pill or 2 days for the progestogen-only pill).
Lactational amenorrhea is over 98% effective as contraception for up to 6 months after birth. Women must be fully breastfeeding and amenorrhoeic (no periods).
The progestogen-only pill and implant are considered safe in breastfeeding and can be started at any time after birth.
The combined contraceptive pill should be avoided in breastfeeding (UKMEC 4 before 6 weeks postpartum, UKMEC 2 after 6 weeks).
A copper coil or intrauterine system (e.g. Mirena) can be inserted either within 48 hours of birth or more than 4 weeks after birth (UKMEC 1), but not inserted between 48 hours and 4 weeks of birth (UKMEC 3).
What barrier methods of contraception are available?
- Condoms
Standard condoms are made of latex. Using oil-based lubricants can damage latex condoms and make it more likely they will tear. Polyurethane condoms can be used in latex allergy. - Diaphragms and Cervical Caps
Diaphragms and cervical caps are silicone cups that fit over the cervix and prevent semen from entering the uterus. The woman fits them before having sex, and leaves them in place for at least 6 hours after sex. They should be used with spermicide gel the further reduce the risk of pregnancy.
When used perfectly with spermicide, diaphragms and cervical caps are around 95% effective at preventing pregnancy. They offer little protection against STIs, and condoms need to be used for STI protection. - Dental Dams
Dental dams are used during oral sex to provide a barrier between the mouth and the vulva, vagina or anus. They are used to prevent infections that can be spread through oral sex, including:
-Chlamydia
-Gonorrhoea
-Herpes simplex 1 and 2
-HPV (human papillomavirus)
-E. coli
-Pubic lice
-Syphilis
-HIV
What is the mechanism of action of the combined oral contraceptive pill (COCP)?
The combined oral contraceptive pill (COCP) contains a combination of oestrogen and progesterone. The combined pill is more than 99% effective with perfect use, but less effective with typical use (91%). The pill is licensed for use up to the age of 50 years.
Mechanism of Action
The COCP prevents pregnancy in three ways:
1. Preventing ovulation (this is the primary mechanism of action)
2. Progesterone thickens the cervical mucus
3. Progesterone inhibits proliferation of the endometrium, reducing the chance of successful implantation
Oestrogen and progesterone have a negative feedback effect on the hypothalamus and anterior pituitary, suppressing the release of GnRH, LH and FSH. Without the effects of LH and FSH, ovulation does not occur. Pregnancy cannot happen without ovulation.
The lining of the endometrium is maintained in a stable state while taking the combined pill. When the pill is stopped the lining of the uterus breaks down and sheds. This leads to a “withdrawal bleed“. This is not classed as a menstrual period as it is not part of the natural menstrual cycle. “Breakthrough bleeding” can occur with extended use without a pill-free period.
What are the types of combined oral contraceptive pill (COCP) and in which cases are they more indicated?
There are two types of COCP to be aware of:
1. Monophasic pills contain the same amount of hormone in each pill
2. Multiphasic pills contain varying amounts of hormone to match the normal cyclical hormonal changes more closely
Everyday formulations (e.g. Microgynon 30 ED) are monophasic pills, but the pack contains seven inactive pills, making it easier for women to keep track by simply taking the pills in order every day.
Different formulations vary in the amount of oestrogen (ethinylestradiol) and the type of progesterone they contain. Examples of monophasic combined contraceptive pills are:
-Microgynon contains ethinylestradiol and levonorgestrel
-Loestrin contains ethinylestradiol and norethisterone
-Cilest contains ethinylestradiol and norgestimate
-Yasmin contains ethinylestradiol and drospirenone
-Marvelon contains ethinylestradiol and desogestrel
- The NICE Clinical Knowledge Summaries (2020) recommend using a pill with levonorgestrel or norethisterone first line (e.g. Microgynon or Leostrin). These choices have a lower risk of venous thromboembolism.
- Yasmin and other COCPs containing drospirenone are considered first-line for premenstrual syndrome. Drospirenone has anti-mineralocorticoid and anti-androgen activity, and may help with symptoms of bloating, water retention and mood changes. Continuous use of the pill, as opposed to cyclical use, may be more effective for premenstrual syndrome.
- Dianette and other COCPs containing cyproterone acetate (i.e. co-cyprindiol) can be considered in the treatment of acne and hirsutism. Cyproterone acetate has anti-androgen effects, helping to improve acne and hirsutism. The oestrogenic effects mean that co-cyprindiol has a 1.5 – 2 times greater risk of venous thromboembolism compared to the first-line combined pills (e.g. Microgynon). It is usually stopped three months after acne is controlled, due to the higher risk of VTE.
What are the possible regimes for combined oral contraceptive pill treatments?
The combined pill can be taken in different regimes to suit the individual. These regimes are equally safe and effective. Three common options are:
-21 days on and 7 days off
-63 days on (three packs) and 7 days off (“tricycling“)
-Continuous use without a pill-free period
What are the side effects and risks of the combined oral contraceptive pill (COCP)?
-Unscheduled bleeding is common in the first three months and should then settle with time
-Breast pain and tenderness
-Mood changes and depression
-Headaches
-Hypertension
-Venous thromboembolism (the risk is much lower for the pill than pregnancy)
-Small increased risk of breast and cervical cancer, returning to normal ten years after stopping
-Small increased risk of myocardial infarction and stroke
What are the benefits of the combined oral contraceptive pill?
The benefits of the combined pill include:
-Effective contraception
-Rapid return of fertility after stopping
-Improvement in premenstrual symptoms, menorrhagia (heavy periods) and dysmenorrhoea (painful periods)
-Reduced risk of endometrial, ovarian and colon cancer
-Reduced risk of benign ovarian cysts
What are the contraindications to using the combined oral contraceptive pill (COCP)?
When starting any form of contraception, it is essential to consider the contraindications for the individual. There are specific risk factors that should make you avoid the combined contraceptive pill (UKMEC 4):
-Uncontrolled hypertension (particularly ≥160 / ≥100)
-Migraine with aura (risk of stroke)
-History of VTE
-Aged over 35 and smoking more than 15 cigarettes per day
-Major surgery with prolonged immobility
-Vascular disease or stroke
-Ischaemic heart disease, cardiomyopathy or atrial fibrillation
-Liver cirrhosis and liver tumours
-Systemic lupus erythematosus (SLE) and antiphospholipid syndrome
-It is worth noting that a BMI above 35 is UKMEC 3 for the combined pill (risks generally outweigh the benefits).
What are the rules for starting the combined oral contraceptive pill (COCP) and for switching between pills?
Start on the first day of the cycle (first day of the menstrual period). This offers protection straight away. No additional contraception is required if the pill is started up to day 5 of the menstrual cycle.
Starting after day 5 of the menstrual cycle requires extra contraception (i.e. condoms) for the first 7 days of consistent pill use before they are protected from pregnancy. Ensure the woman is not already pregnant before starting the pill (i.e. they have been using contraception reliably and consistently).
When switching between COCPs, finish one pack, then immediately start the new pill pack without the pill-free period.
When switching from a traditional progesterone-only pill (POP), they can switch at any time but 7 days of extra contraception (i.e. condoms) is required. Ensure the woman is not already pregnant before switching (i.e. they have been using contraception reliably and consistently).
When switching from desogestrel, they can switch immediately, and no additional contraception is required. This differs from a traditional POP because desogestrel inhibits ovulation.
What are the important points in a consultation with a patient when prescribing the combined oral contraceptive pill (COCP)?
There are several things to check and discuss when prescribing the combined pill:
-Different contraceptive options, including long-acting reversible contraception (LARC)
-Contraindications
-Adverse effects
-Instructions for taking the pill, including missed pills
-Factors that will impact the efficacy (e.g. diarrhoea and vomiting)
-Sexually transmitted infections (this pill is not protective)
-Safeguarding concerns (particularly in those under 16)
Screen for contraindications by discussing and documenting:
-Age
-Weight and height (BMI)
-Blood pressure
-Smoker or non-smoker
-Past medical history (particularly migraine, VTE, cancer, cardiovascular disease and SLE)
-Family history (particularly VTE and breast cancer)
What are the missed pill rules for the combined oral contraceptive pill (COCP)?
The best way to understand the rules is to consider that theoretically women will be protected if they perfectly take the pill in a cycle of 7 days on, 7 days off. This will prevent ovulation.
Missing one pill is when the pill is more than 24 hours late (48 hours since the last pill was taken).
Missing one pill (less than 72 hours since the last pill was taken):
-Take the missed pill as soon as possible (even if this means taking two pills on the same day)
-No extra protection is required provided other pills before and after are taken correctly
Missing more than one pill (more than 72 hours since the last pill was taken):
-Take the most recent missed pill as soon as possible (even if this means taking two pills on the same day)
-Additional contraception (i.e. condoms) is needed until they have taken the pill regularly for 7 days straight
If day 1 – 7 of the packet they need emergency contraception if they have had unprotected sex
If day 8 – 14 of the pack (and day 1 – 7 was fully compliant) then no emergency contraception is required
If day 15 – 21 of the pack (and day 1 – 14 was fully compliant) then no emergency contraception is needed. They should go back-to-back with their next pack of pills and skip the pill-free period.
Theoretically, additional contraception is not required if more than one pill is missed between day 8 – 21 (week 2 or 3) of the pill packet and they otherwise take the pills correctly, although it is recommended for extra precaution.
What factors affect the efficacy of the combined oral contraceptive pill (COCP) and when should the pill be stopped before surgery?
Vomiting, diarrhoea and certain medications (e.g. rifampicin) can all reduce the effectiveness of the pill, and additional contraception may be required. A day of vomiting or diarrhoea is classed as a “missed pill” day, as the illness may affect the absorption.
NICE Clinical Knowledge Summaries (January 2019) recommends stopping the combined pill four weeks before a major operation (lasting more than 30 minutes) or any operation or procedure that requires the lower limb to be immobilised. This is to reduce the risk of thrombosis.
How is the progestogen-only pill taken and when is it contraindicated?
The progestogen-only pill (POP) is a type of contraceptive pill that only contains progesterone. The POP is taken continuously, unlike the cyclical combined pills. It is more than 99% effective with perfect use, but less effective with typical use (91%).
The progestogen-only pill has far fewer contraindications and risks compared with the combined pill. The only UKMEC 4 criteria for the POP is active breast cancer.
What are the two types of progestogen-only pill?
There are two types of POP to remember:
1. Traditional progestogen-only pill (e.g. Norgeston or Noriday)
2. Desogestrel-only pill (e.g. Cerazette)
The traditional progestogen-only pill cannot be delayed by more than 3 hours. Taking the pill more than 3 hours late is considered a “missed pill”.
The desogestrel-only pill can be taken up to 12 hours late and still be effective. Taking the pill more than 12 hours late is considered a “missed pill”.
What is the mechanism of action of the progestogen-only pill?
Traditional progestogen-only pills work mainly by:
-Thickening the cervical mucus
-Altering the endometrium and making it less accepting of implantation
-Reducing ciliary action in the fallopian tubes
Desogestrel works mainly by:
-Inhibiting ovulation
-Thickening the cervical mucus
-Altering the endometrium
-Reducing ciliary action in the fallopian tubes
What are the rules for starting the progestogen-only pill?
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.)
What are the rules for switching between progestogen-only pills or switching from COCP to POP?
- Switching between POPs
POPs can be switched immediately without any need for extra contraception. - 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.
What are the side effects and risks when using the progestogen-only pill?
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
What are the rules for missed pills when taking the progestogen-only pill?
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.
What is the progestogen-only injection? What are the types?
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.
What are the contraindications to the depot injection?
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.
What is the mechanism of action of the depot injection?
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
When are depot injections times for contraceptive cover?
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.
What are the side effects and risks of the contraceptive depot injection?
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)
What are the potential benefits of the contraceptive depot injection?
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
What is the progesterone-only implant and what is its mechanism of action? What is the contraindication?
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
What are the considerations for insertion and removal of the contraceptive implant?
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).
What are the benefits of the contraceptive implant?
-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)
What are the disadvantages of the contraceptive implant?
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.
What are the types of intrauterine devices?
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”.
What are the contraindications to the use of intrauterine devices?
-Pelvic inflammatory disease or infection
-Immunosuppression
-Pregnancy
-Unexplained bleeding
-Pelvic cancer
-Uterine cavity distortion (e.g. by fibroids)
What does the process of intrauterine device insertion involve and what are the risks?
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
What are the possible causes for non-visible intrauterine device threads and what actions should be taken?
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.
What are the rules surrounding intrauterine device removal?
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.
What is the mechanism of action of the copper coil?
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.
What are the benefits of the copper coil?
-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
What are the drawbacks to the copper coil?
-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.
What are the types of Levonorgestrel intrauterine device?
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.
What is the mechanism of action of the levonorgestrel intrauterine device?
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.
What are the benefits of the hormonal coil?
-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)
What are the drawbacks to using the hormonal contraceptive coil?
-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.
What emergency contraception options are available?
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
What considerations should be made when choosing the method of emergency contraception?
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
How does the copper coil work as emergency contraception and what are the rules and risks?
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.
How does levonorgestrel work as emergency contraception and what are the rules and side effects/risks?
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.
How does Ulipristal work as emergency contraception and what are the rules and side effects/risks?
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
What are the types of sterilisation procedures for men and women?
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.
- 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.
What is Gillick competence?
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.
What are the Frazer guidelines?
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:
- They are mature and intelligent enough to understand the treatment
- They can’t be persuaded to discuss it with their parents or let the health professional discuss it
- They are likely to have intercourse regardless of treatment
- Their physical or mental health is likely to suffer without treatment
- Treatment is in their best interest
- 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.
When is investigation and referral for infertility initiated?
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.
What are the possible causes of infertility?
- Sperm problems (30%)
- Ovulation problems (25%)
- Tubal problems (15%)
- Uterine problems (10%)
- Unexplained (20%)
40% of infertile couples have a mix of male and female causes.
What general lifestyle advice can be given to couples trying to get pregnant?
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.
How is infertility investigated?
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:
- 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). - 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.
- 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.
- Thyroid function tests when symptoms are suggestive
- 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
What does a hysterosalpingogram for infertility involve?
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.
What does a laparoscopy and dye test for infertility involve?
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.
What are the management options when anovulation is the cause of infertility?
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.
What are the management options when tubal or uterine factors are the cause of infertility?
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.
What are the management options when sperm problems are the cause of infertility?
- 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.
- Surgical correction of an obstruction in the vas deferens may restore male fertility.
- 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.
- 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.
- Donor insemination with sperm from a donor is another option for male factor infertility.
What are the rules for men providing a sample for semen analysis
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
What factors can affect semen analysis and sperm quality and quantity?
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.
What are the possible results from semen analysis?
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%)
- Polyspermia (or polyzoospermia) refers to a high number of sperm in the semen sample (more than 250 million per ml).
- Normospermia (or normozoospermia) refers to normal characteristics of the sperm in the semen sample.
- 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). - Azoospermia is the absence of sperm in the semen.
What are the possible causes of male factor infertility?
- 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 - 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)
- 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)
What investigations are required following an abnormal semen sample?
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
How is male factor infertility managed?
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
What is the process of egg collection for IVF?
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.
- 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.
- 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”.
- 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.
What is the process of fertilisation , embryo transfer and pregnancy testing in IVF?
- 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.
- 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). - 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. - 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.
What are the complications and risks of IVF?
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
What is ovarian hyperstimulation syndrome?
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.
What is the pathophysiology of ovarian hyperstimulation syndrome?
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.
What are the risk factors for ovarian hyperstimulation syndrome?
-Younger age
-Lower BMI
-Raised anti-Müllerian hormone
-Higher antral follicle count
-Polycystic ovarian syndrome
-Raised oestrogen levels during ovarian stimulation
How can ovarian hyperstimulation syndrome be prevented?
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)
What are the clinical features of ovarian hyperstimulation syndrome?
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)
How is the severity of ovarian hyperstimulation syndrome ranked?
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)
How is ovarian hyperstimulation syndrome managed?
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.
What is an ectopic pregnancy?
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.
What are the risk factors for ectopic pregnancies?
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
What are the presenting features of ectopic pregnancies?
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)
What would be the ultrasound findings in an ectopic pregnancy?
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”)
What is a pregnancy of unknown location and what are the telling signs?
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.
How are ectopic pregnancies managed?
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)
What are the criteria for expectant management of an ectopic pregnancy?
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.
What are the criteria for management of an ectopic pregnancy with methotrexate? What are the rules, risks and side effects?
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)
What are the criteria for surgical management of an ectopic pregnancy and what are the types?
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.
What is a miscarriage and what are the types?
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
What are the ultrasound findings in a miscarriage?
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.
