Subfertility Flashcards
Define
Subfertility = a woman of reproductive age that has not conceived after 1 year of regular, unprotected sexual intercourse
- Chances of getting pregnant 19-26yo = 98% over 24 months (twice weekly unprotected sexual intercourse)
- Sub-fertility affects 1 in 6 couples (incidence increases with maternal age)
Types:
- PRIMARY- couples that have never conceived together
- SECONDARY- couples who have previously conceived together
Causes of subfertility:
- Female problem = 30-40%
- Unexplained = 30%
- Male problem = 25-30%
Aetiology - Female causes
Ovulatory disorders (25%)
Group 1: Hypothalamic-pituitary failure (hypogonadotropic hypogonadism)
- Low gonadotrophins and low oestrogen
- Low weight, excessive exercise, Kallman’s syndrome, Sheehan’s syndrome
Group 2: Hypothalamic-pituitary-ovarian dysfunction (normogonadotrophic normogonadism)
- Normal gonadotrophins, normal oestrogen
- PCOS – most COMMON cause of ovulate ray dysfunction
Group 3: Ovarian Failure (hypergonadotrophic hypogonadism)
- High gonadotrophins, low oestrogen
- POI (amenorrhoea of 4 months, <40yo, FSH high on 2 consecutive tests)
Group 4: Prolactinaemia, Thyroid Disease
- Prolactinoma, primary hypothyroidism, chronic renal failure, drugs
Tubular problems (20%)
Blockage is associated with inflammatory disorders e.g.:
- Pelvic Inflammatory Disease
Chlamydia
- Can affect the tubes and surrounding structures
- May get peri-hepatitis (Fitz-Hugh-Curtis syndrome)
Gonorrhoea
- Usually affects the tubes
Endometriosis
Previous pelvic or abdominal surgery – resulting in scar tissue or adhesions
- Appendicectomy
- Surgical termination of pregnancy
- Removal of ectopic pregnancy
Hydrosalpinx
- Low preg rates even with IVF!
Uterine/ Cervical problems (10%)
Fibroids
- Submucosal – have an impact on embryo implantation
- Intramural – may reduce fertility if large
- Subserosal – have little impact
Endometrial polyps may reduce chance of implantation
Endometrial scarring (Asherman’s syndrome) from surgery or infection can lead to lighter periods and a significantly reduced chance of conception
Congenital abnormalities
- Arcuate uterus - does NOT increase chance of miscarriage or affect fertility
- bicornuate uterus - correcting for doesn’t improve chance of fertility as surgery is so traumatic
- Unicornuate uterus - correcting for doesn’t improve chance of fertility as surgery is so traumatic
- Septate uterus - can resect to improve chances
Aetiology - Male causes (30% of causes)
Idiopathic (44%)
Reduced sperm quality and quantity
- Microdeletions of AZF regions on Y chromosome associated with low sperm counts and motility
Spermatogonial cells may be damaged from inflammation or damage to epididymis (responsible for storing mature sperm)
Obstructive azoospermia
Varicocele
Hypogonadism
Diabetes mellitus
Contact with chemicals or radiation, pelvic radiotherapy or surgery
Aneuploidy of sex chromosomes e.g.
- Klinefelter (XXY)
- Structural abnormalities of autosome e.g. inversions, deletions or balanced translocations
Aetiology - Unexplained/ Unidentifiable (25%)
Any IU devices
Contraceptives
- With progesterone only injectable contraception there can be a delay in return to natural fertility of up to 12 months. The other methods are not associated with such a delay.
Considerations for early referral
Risk factors
Female
- Age > 35 years
- History of STI
- High BMI
- Low BMI
- Cigarette smoking
- History of prior pelvic surgery
Male
- Varicocele
- Cryptorchidism
- Prior radiotherapy or chemotherapy
- Current medications
- CF or CBAVD
- Y chromosome abnormalities- microdeletions
- Endocrinopathy e.g. low Testosterone levels, low FSH/ LH secretion or function, hyperprolactinaemia, gonadotrophin deficiency
Signs and symptoms
Presenting Symptoms
- Irregular menstrual cycles
- History of previous pelvic surgery e.g. myomectomy, ovarian cystectomy
- Palpable and dilated testicular veins
- Erectile dysfunction and decreased libido
Signs O/E
- Acne
- Hirsutism
- Palpable uterine abnormalities
- Adnexal abnormalities
- Testis atrophy (< 20cm3)
Investigations
full history -> duration and type of infertility, coital frequency, menstrual history, PCOS symptoms, contraceptive history, previous STI, PMHx, PSHx, DHx, SHx (alcohol and smoking):
1st line basic tests (men and women):
Male:
- Semen analysis (2 tests, 3m apart) – if azoospermia, most commonly due to varicocele
- Chlamydia screen
Female:
- Mid-luteal (day 21) progesterone (confirm ovulation) à >30 indicated ovulation
- Adjust if cycle >28 days o If POI, you cannot do this as there are no periods to base the measurement off
- Chlamydia screen
- Other -> prolactin, TFTs, progesterone (prolonged irregular cycles), LH/FSH (irregular cycles)
Ovarian reserve measure (≥1 of 3 results measures around day 3 of the cycle):
- FSH à raised; inaccurate during the luteal phase (being supressed by progesterone)
- Anti-Mullerian hormone (AMH) à low; does not change with cycles so taken anytime
- TVUSS à Antral Follicle Count (AFC: <4 = poor response; 16+ = good response)
Tubal assessment:
- No co-morbidities -> hysterosalpingography / HSG à assess patency
- Co-morbidities (hx of PID, ectopics, endometriosis) à laparoscopy and dye
Management
1st line: wait for regular intercourse to be established for at least 12 months (every 2-3 days)
- Key Information: BMI 20-25, folic acid, regular intercourse (every 2-3 days), smoking/drinking advice
- Ix -> perform investigations after 12 months…
2nd line: unexplained sub-fertility, mild endometriosis, or ‘male factor’ sub-fertility -> try for another 12m
- After this, you can consider IVF
Medical management for fertility:
- Ovulation induction -> anovulation (PCOS, idiopathic):
· 1st line: clomiphene (blocks oestrogen-R à increased LH/FSH release)
· 2nd line: FSH and LH injections
· 3rd line: pulsatile GnRH or DA agonists
Surgical management for fertility:
- Operative laparoscopy -> adhesions, ovarian cyst, endometriosis
- Myomectomy -> fibroids
- Tubal surgery -> blocked tubes amenable to repair
- Laparoscopic ovarian drilling -> PCOS (unresponsive to medical management)
- Removes endometrium à reduce amount of androgen-producing tissue
Assisted conception:
Intrauterine insemination ± LH/FSH -> idiopathic, anovulation unresponsive to OI, mild male factor, minimal to mild endometriosis (sperm placed in uterus with fine plastic tube at time of ovulation)
IVF -> blocked tubes, male minor factor, idiopathic, unsuccessful OI or intrauterine insemination
- Leave the egg and sperm in a petri dish and they fertilise each other
- Availability is decided trust-by-trust (i.e. a postcode lottery) – NICE guidance:
Women <40 offered 3 cycles of IVF if…
- Subfertility for 2 years
- Not pregnant after 12 cycles of artificial/intrauterine insemination
Women 40-42 offered 1 cycle of IVF if…
- Subfertility for 2 years and/or not pregnant after 12 cycles of AI
- Never had IVF
- No evidence of low ovarian reserve
- Informed about additional implications of IVF at this age
Intracytoplasmic sperm injection (ICSI) à oligospermia, poor fertilisation (DM, erectile dysfunction)
- · Most common treatment for male infertility
- · Sperm directly injected into the egg (bypass natural barriers)
Donor insemination ± LH/FSH à azoospermia, single women, same sex couples, infectious disease
Donor egg with IVF à POI, bilateral oophorectomy, gonadal dysgenesis, high-risk generic disorder
Complications
Ovulation induction (from multiple eggs in multiple pregnancy)
Ovarian Hyperstimulation Syndrome (ovaries become hyperstimulated à exposure to hCG -> pro-inflammatory mediators -> ovarian enlargement, increased vascular permeability (third spacing), prothrombotic state)
- S/S: abdominal pain + distension, N+V, SOB, oedema/ascites
- Management: Symptomatic management, fluid replacement, VTE prophylaxis
Ectopic pregnancy
Pelvic infection
Multiple gestation
Increased cancer risk- Ovarian, Testicular
PACES
Risk Factors: advanced maternal age, smoking and alcohol use, obesity, irregular periods, STI
Explain that there is still a chance of getting pregnant naturally (15% of couples fail to conceive after 1 year)
Explain that you would like to start investigations (blood test looking at hormone levels, USS looking at structure of the uterus and follicle count and HSG if there are risk factors)
Encourage regular unprotected sex at least every other day (not too much à let sperm count recover)
Discuss management options depending on likely cause of subfertility
Infertility - female summary
Infertility - male summary
