Infertility Flashcards

1
Q

What percent of patients will concieve within a year of regular unprotected sex?

A

85%

Regular = 2-3 times a week

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2
Q

What proportion of couples will struggle to conceive naturally?

A

1 in 7

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3
Q

When should investigation and referreal for infertility be initiated?

A

After the couple has been trying to conceieve without success for 12 months (this can be reduced to 6 months if the woman is older than 35 as her ovarian stores are already reduced and time is more precious)

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4
Q

What are some causes of infertility?

A

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

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5
Q

What is some general lifestyle advice for couples trying to get pregnant?

A

Woman should be taking 400mcg of Folic acid daily

Aim for healthy BMI

Avoid smoking and drinking excessive alcohol

Reduce stress as this may negatively affect libido and the relationship

Avoid timing intercourse

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6
Q

What are some initial investigations in primary care for infertility?

A

BMI (low indicates anovulation, high indicates PCOS)

Chlamydia screening

Semen analysis

Female hormonal testing

Rubella immunity in the mother

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7
Q

What does female hormone testing for infertility involve?

A

Serum LH and FSH on day 2 to 5 of the cycle

Serum progesterone on day 21 of the cycle (or 7 days before the end of the cycle if not a 28-day cycle).

Anti-Mullerian hormone

Thyroid function tests when symptoms are suggestive

Prolactin (hyperprolactinaemia is a cause of anovulation) when symptoms of galactorrhea or amenorrhoea

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8
Q

What does a high FSH indicate for infertilty?

A

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.

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9
Q

What does a high LH suggest for infertility?

A

Polycystic ovarian syndrome

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10
Q

What does a rise in progesterone on day 21 indicate?

A

That ovulation has occurred and the corpus luteum has formed secreting progesterone

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11
Q

Why is anti-mullerian hormone measured in infertility?

A

Most accurate marker of ovarian reservereleased by the granulosa cells in the follicles and falls as the eggs are depleted – high level indicates a good ovarian reserve

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12
Q

What are some further investigations in primary care for infertility?

A

Ultrasound pelvis to look for polycystic ovaries or any structural abnormalities

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

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13
Q

What is a hysterosalpingogram?

A

Scan used to assess the shape of the uterus and patency of the fallopian tubes – helps with diagnosis and has a therapeutic benefit – increases the rate of conception without any other intervention

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14
Q

What intervention can be performed during a hysterosalpingogram?

A

Tubal cannulation under x-ray guidance – to open the tubes

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15
Q

How is a hysterosalpingogram performed?

A

Small tube is inserted into the cervix and a contrast medium injected through the tube – fills uterine cavity and fallopian tubes – x-ray images are then taken

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16
Q

What are the risks of hysterosalpingogram?

A

Risk of infection with the procedure and often antibiotics are given prophylactically for patients with dilated tubes / history of pelvic infection

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17
Q

What should be screened for before a hysterosalpingogram?

A

Chlamydia and gonorrhoea

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18
Q

What is involved in a laparoscopy and dye test?

A

Dye is injected into the uterus and should be seen entering the tubes and spilling out at the ends – during laparoscopy the surgeon can also assess for endometriosis or pelvic adhesions and treat these

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19
Q

What are the management options for anovulation?

A

Weight loss for overweight patients with PCOS can restore ovulation

Clomifene

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)

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20
Q

How does clomifene help with anovlation?

A

It’s an anti-oestrogen given on day 2-6 of the menstrual cycle – stops the negative feedback of oestrogen on the hypothalamus resulting in a greater release of GnRH and subsequently FSH and LH

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21
Q

How can ovarian drilling help with infertility?

A

Laparoscopic surgery where the surgeon punctures multiple holes in the ovaries using diathermy or laser therapy – improving the womans hormonal profile and resulting in regular ovulation and fertility

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22
Q

How are tubal factors for women with infertility managed?

A

Tubal cannulation during hysterosalpingogram

Laparoscopy to remove adhesions or endometriosis

In vitro fertilisation (IVF)

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23
Q

How are uterine factors managed in infertility?

A

Surgery to correct polyps, adhesions or structural abnormalities affecting fertility

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24
Q

What are the management options for sperm problems in infertility?

A

Surgical sperm retrieval

Surgical correction of an obstruction in the vas

Intra-uterine insemination (ICSI)

Intracytoplasmic sperm injection

Donor insemination

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25
What is surgical sperm retrieval?
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** from the **epididymis** through the scrotum
26
What does intra-uterine insemination involve?
Collecting and separating out **high quality sperm** then **injecting** them **directly** into the **uterus of the woman** (unclear if this is any better than normal intercourse)
27
What is intracytoplasmic sperm injection?
**Injecting sperm** directly **into the cytoplasm of an egg** – **fertilised eggs become embryos** and are **injected into the uterus of a woman** – useful when there are significant motility issues and a very low sperm count along with other issues
28
What is donor insemination?
Using **sperm from a donor** is another option for male factor infertility
29
How can semen analysis help with infertility issues?
Used to **examine the quantity and quality of the semen** and sperm – assesses for male factor infertility
30
What instructions are men given on sperm samples?
**Abstain from ejaculation** for **at least 3 days** and at most 7 days **Avoid hot baths, sauna and tight underwear f**or 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
31
What factors may affect semen analysis?
Hot baths Tight underwear Smoking Alcohol Raised BMI Caffeine
32
When will a repeat semen sample be needed?
**After 3 months** in borderline results or 2-4 weeks with very abnormal results
33
What are normal sperm results according to the WHO?
**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%**)
34
What is polyspermia?
**High number of sperm** in the semen sample (more than 250 million per ml)
35
What is normospermia?
Refers to **normal characteristics of the sperm** in the semen sample
36
What is oligospermia?
**Reduced number of sperm in the semen sample**, classified as: **Mild** oligospermia (10 to 15 million / ml) **Moderate** oligospermia (5 to 10 million / ml) **Severe** oligospermia (less than 5 million / ml)
37
What is **cryptozoospermia**?
**Very few sperm** in the semen sample (less than 1 million / ml)
38
What are some causes of reduced sperm quality or quantity?
Hot baths Tight underwear Smoking Alcohol Raised BMI Caffeine
39
What are some pretesticular causes of reduced sperm quality or quantity?
**Pathology of the pituitary gland / hypothalamus** **Suppression due to stress, chronic conditions or hyperprolactinaemia** **Kallman syndrome** **Causing hypogonadotrophic hypogonadism** (low LH and FSH resulting in low testosterone – necessary for sperm production)
40
What are some causes of testicular damage causing male infertility?
**Mumps** **Undescended testes** **Trauma** **Radiotherapy** **Chemotherapy** **Cancer**
41
What are some genetic or congenital disorders that result in defective or absent sperm production?
**Klinefelter** syndrome **Y** chromosome **deletions** **Sertoli cell-only syndrome** Anorchia **(absent testes)**
42
What are some obstructive causes of male infertility?
**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)
43
What are the initial steps for investigating abnormal semen analysis?
**History** **Examination** **Repeat sample** **Ultrasound of testes**
44
What further investigations may be done on a semen sample?
**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**
45
What is the management of male infertility?
Depends on the **underlying cause:** **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
46
How does IVF work?
**Fertilising an egg** with a sperm in a lab and then **injecting** the resulting **embryo** into the uterus – **funding criteria are strict** and vary between areas – couples are limited to a set number of cycles funded by the NHS
47
What is the **success rate of IVF?**
25-30% success rate at producing a live birth
48
How is intrauterine insemination different from IVF?
**More straightforward process** and involves injecting sperm directly into the uterus avoiding intercourse – used in cases such as donor sperm for same-sex couples, HIV (avoiding unprotected intercourse) and practical issues with vaginal sex
49
How does IVF work? Can embryos be used later on?
**Cycle of IVF** involves a single episode of ovarian stimulation and collection of oocytes (eggs) – single cycle may produce **several embryos** Embryos can be **transferred separatley** in **multiple attempts at pregnancy** during one "cycle" of IVF - embryos that are not used immediately can be frozen to be **used at later date** - frozen embryos can potentially be used **years later**
50
What are the steos involved in IVF?
**Suppressing the natural menstrual cycle** **Ovarian stimulation** **Oocyte collection** **Insemination** / intracytoplasmic sperm injection (ICSI) **Embryo culture** **Embryo transfer**
51
What are the 2 protocols for **suppressing the natural menstrual cycle, preventing ovulation** and ensuring the **ovaries respond correctly to the gonadotrophins (ie FSH)**?
GnRH agonist or GnRH antagonist
52
How does the **GnRH agonist protocol work** to suppress the natural menstural cycle?
Injection of GnRH agonist (e.g. goserelin) is given in the **luteal phase** of the menstural cycle (around 7 days before expected onset of menstrual period) usually **day 21 of the cycle** Stilulates the **pituitary gland** to **secrete a large amount of FSH and LH** after this initial surge there is **negative feedback** to the hypothalamus and the natural production of **GnRH** is **suppressed** - causing **suppression of menstrual cycle**
53
How does the **GnRH protocol** work to suppress the natural menstrual cycle?
Daily **subcutaneous** injections of a **GnRH antagonist** (e.g. cetrorelix) are given starting from day 5-6 of ovarian stimulation - supresses the body releasing LH and causing ovulation to occur
54
Why is **suppression of the natural gonadotrophins (LH and FSH) needed in IVF**?
**Follicles** which are developing would be **released** before it is possible to collect them
55
How does **ovarian stimulation** work in IVF?
Using medications to **promote** the development of **multiple follicles** in the ovary - starting at **beginning of the menstrual cycle** (usually day 2) with **subcutaneous** injections of **FSH** over 10 to 14 days - FSH **stimulates** the development of follicles and this is **closely monitored** with **regular transvaginal ultrasound scans**
56
What is the **trigger injection** in ovarian stimulation?
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”.
57
How are **oocytes collected from the ovaries** in IVF?
Under **guidance** of a **transvaginal ultrasound scan** **Needle** is **inserted** through the **vaginal wall into each ovary** to **aspirate** the fluid from **each follicle** Fluid **contains the mature oocyte** from the follicles Procedure is usually performed under **sedation** (not general anaesthetic) - fluid from the follicles is **examined under the microscope for oocytes**
58
How does **oocyte insemination** work in IVF?
Male produces a **semen sample** around the time of **oocyte collection** - **frozen sperm** from **earlier** samples may be used - sperm and egg are mixed in a culture medium - **thousands of sperm** need to be **combined** with each oocyte **to produce enough enzyme**s (e.g. **hyaluronic acid**) for one sperm to penetrate the **corona radiata** and **zona pellucida** and **fertilise the egg**
59
When is **intracytoplasmic** sperm injection used?
**Male factor infertility**
60
How does intracytoplasmic sperm injection work?
In **addition to the IVF process** - after the eggs are harvested a semen sample is produced **the highest quality sperm are isolated** and **injected** directly into the **cytoplasm of the egg**
61
How long does the embryo culture take? What happens?
**2 - days** left in an incubator to see which grow into a **blastocyst** stage of development
62
How does the **embryo transfer** work in **IVF**?
After 2-5 days the **highest quality embryos** are **selected** for transfer - **catheter is inserted** under **ultrasound guidance** through the cervix and **into the uterus** - a **single** embryo is injected through the catheter - generally a single embryo is transferred but **2 may be transferred in older women** (i.e. over 35 years) any **remaining embryos** can be **frozen** for future attempts
63
When is a pregnancy test performed after egg collection? What could go wrong?
**16 days** after egg collection - when this is **positive** implantation has occured There is the **possibility** of **miscarriage** or **ectopic pregnancy**
64
What happens if a pregnancy test is negative after implantation?
**Hormonal treatment is stopped** - woman will go on to have a menstrual period - **bleeding may be more substantial** than usual **given the additional hormones** used during ovarian stimuation
65
How is progesterone given after IVF embryo implantation?
From oocyte collection until 8-10 weeks gestation usually in the form of **vaginal suppositories** in order to **mimic** the progesterone that would be released by the **corpus luteum** during a typical pregnancy (after which the **placenta** takes over the production of progesterone)
66
In IVF, when is an ultrasound scan performed to confirm a fetal heartbeat?
Around **7 weeks** (also to rule out miscarriage or ectopic pregnancy) - if this is healthy then the remainder of the pregnancy can proceed with **standard care**
67
What are the main complications of IVF?
**Failure** **Multiple pregnancy** **Ectopic** pregnancy **Ovarian hyperstimulation syndrome**
68
What are the risks of the egg collection procedure?
**Pain** **Bleeding** Pelvic **infection** **Damage to the bladder** or bowel
69
What is **ovarian hyperstimulation syndrome**?
Complication of ovarian stimulation during IVF infertility treatment - associated with the use of **human chorionic gonadotrophin** to mature the follicles during the final steps of ovarian stimulation
70
What is the **pathophysiology** behind **ovarian hyperstimulation syndrome**?
Increase in **vascular endothelial growth factor** (VEGF) released by the **granulosa cells** of the **follicles** - this **increases vascular permeability** cauing **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 (this **stimulates** the **release of VEGF** from the follicles) There is also **activation of the RAAS** system - notable finding in patients with OHSS is a **raised renin level** which correlates with the severity of the condition
71
What are the risk factors for OHSS?
**Younger age** **Lower BMI** **Raised anti-Müllerian** hormone **Higher antral follicle count** **Polycystic ovarian syndrome** **Raised oestrogen levels** during ovarian stimulation
72
How is OHSS risk monitored?
During stimulation with gonadotrophinc 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)
73
What strategies can be used to reduce the risk of OHSS?
**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)
74
When does OHSS present?
Within 7 days of the hCG injection (early OHSS) Later than 10 days (late OHSS)
75
What are the features of OHSS?
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)
76
What are the symptoms of mild OHSS?
Abdominal pain and bloating
77
What are the symptoms of moderate OHSS?
**Nausea and vomiting** with ascites seen on ultrasound
78
What are the features of severe OHSS?
Ascites, low urine output (oliguria), low serum albumin, high potassium and raised haematocrit (\>45%)
79
What are the features of **critical OHSS**?
**Tense ascites**, **no urine output** (anuria), thromboembolism and acute respiratory distress syndrome (ARDS)
80
What is the management of OHSS?
Supportive with treatment of any complications, involving:
81
How is OHSS managed?
**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)
82
Where are patients with OHSS managed?
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).**
83
How to assess dehydration in OHSS?
**Raised** **haematocrit** can indicate dehydration - this is the **concentration of RBCs in the blood** If its raised this indicated **less fluid in the intravascular space** as the blood is becomming more concentrated