Infertility Flashcards
What % of couples are affected by infertility?
15%
What is the cumulative spontaneous pregnancy rate for women under 40 years old at 1 and 2 years of trying?
1 year: 85%
2 years: 92%
Outline the aetiology of female factor infertility:
- Anovulation:
- Ovarian dysfunction: PCOS.
- Hypergonadotrophic hypogonadism: primary ovarian insufficiency, resistant ovary syndrome
- Hypogonadotrophic hypogonadism: HPA stress, surgery/irradiation to anterior pituitary, inflammation, Sheehan’s syndrome, congenital deficiency (Kallmann’s syndrome).
- Other: hyperprolactinaemia, hypothyroidism - Tubal factor:
- Infection
- Iatrogenic
- Endometriosis - Uterine factor:
- Intrauterine adhesions: infection, Asherman’s syndrome
- Submucous fibroid occluding ostia
- Congenital uterine malformation
Outline the aetiology of male factor infertility:
- Primary testicular dysfunction:
- Failure of spermatogenesis: trauma, infection, cancer, chemotherapy
- Y chromosome microdelections
- Klinefelter’s syndrome XXY - Obstruction:
- Congenital: 10% congenital absence of vas deferens; cystic fibrosis
- Iatrogenic
- Infection - Endocrine:
- Hypogonadotrophic hypogonadism
- Hyperprolactinaemia: causes impotence - Autoimmune: sperm auto-antibodies usually after vasectomy reversal.
- Drugs:
- Recreational: smoking, alcohol, marijuana
- Causing erectile dysfunction: B-blocker, antidepressants
- Reversible: anabolic and corticosteroids, SSZ, antifungals
- Chemotherapy - Environmental: heat, radiation, chemicals
- Varicocoele
What % of men have no predisposing male factor for infertility?
50%
What % of couples have unexplained infertility?
8-28%
What is the % pregnancy rate per cycle of couples with unexplained infertility managed expectantly?
2%
What % of couples with unexplained infertility for <3 years will conceive within 3 years?
60%
What general investigations would you perform as part of your work-up for infertility?
- Rubella immunity status (female)
- HIV, Hep B and C, syphilis serology (both partners).
- Cervical smear
- STI swabs (both partners).
What history would you take from the female in an infertility work-up?
- Age
- Menstrual Hx
- If amenorrhoeic: weight changes, hyperprolactinaemia sx, hypothyroidism sx, menopausal sx.
- GynaeHx
- ObstHx
- Contraception use
- PMedHx and medications
- Drugs: smoking, recreational, alcohol, caffeine.
Outline your examination for a female in an infertility work-up:
- Height, weight, BMI
- Pelvic exam: speculum and bimanual.
- Abdominal exam
- General: signs of endocrine disorders
Outline your investigations for a female in an infertility work-up:
Ovarian reserve:
- Day 2-5 FSH, LH and oestradiol.
- AMH
Ovulation:
- Day 21 progesterone
- TSH, prolactin level
Tubal patency:
- Laparoscopic tubal dye study or HSG or HyCoSy (hysterosalpingo-contrast sonography).
- Pelvic ultrasound
Outline the components of a semen analysis and the normal ranges:
- Volume >1.5 mL
- ph >7.2
- Sperm concentration >15 x 10^6/mL
- Total sperm number >39 x 10^6
- Morphology >4% normal
- Motility >40% motile or 32% progressive motility
- Vitality > 58%
List the investigations you would perform for a male infertility work-up:
- Semen analysis
- Karyotype: cystic fibrosis, Klinefelter syndrome.
- Genetic testing: cystic fibrosis
- FSH and testosterone
- Testicular biopsy: indicate if sperm available for ICSI.
Regarding male factor infertility, outline the type of problem if you had these results:
FSH - normal.
Testosterone - normal.
Obstructive
Regarding male factor infertility, outline the type of problem if you had these results:
FSH - elevated.
Testosterone - normal.
Failure of spermatogenesis
Regarding male factor infertility, outline the type of problem if you had these results:
FSH - elevated.
Testosterone - low.
Complete testicular failure.
Regarding male factor infertility, outline the type of problem if you had these results:
FSH - low.
Testosterone - low.
Hypogonadotrophic hypogonadism
What is your general approach to the management of an infertile couple?
- Normalisation of BMI
- Smoking cessation
- Reduce alcohol intake
- Regular unprotected sexual intercourse every 2-3 days.
What is your approach to the management of an infertile couple with ANOVULATION?
Aim to induce ovulation from a single follicle. Strategies carry risk of multiple pregnancy and OHSS.
Hypogonadotrophic hypogonadism: ovulation induction with daily gonadotrophin injections or pulsatile GnRH infusion.
PCOS:
- Weight reduction
- Clomiphene, letrozole, gonadotrophin injection or pulsatile GnRH
- Metformin
- Surgery: laparoscopic ovarian drilling.
Hypergonadotrophic hypogonadism: ovum donor; no follicles left or ovary not responsive to gonadotrophin.
What are poor prognostic factors of tubal disease where a patient should be referred straight to IVF?
- Luminal adhesions
- Large hydrosalpinx >2 cm
- Thick-walled hydrosalpinx
- Dual blockage (proximal and distal)
- Loss of significant length of tube.
What is your approach to the management of an infertile couple with TUBAL FACTOR infertility?
IVF if unable to repair tubes surgically.
- Bilateral salpingectomy can improve IVF rates.
Surgical repair:
- Success rate for patency 70%
- Pregnancy rate 30%
- Advantages: corrects pathology, may improve other symptoms, cheaper (unlimited attempts to conceive), no increased risk of multiple pregnancies and OHSS, less stress.
- Hydrosalpinx repair: fimbrioplasty most successful 55% pregnancy rate.
- Peritubal adhesions: laparoscopic adhesiolysis, pregnancy rate 60%.
- Reversal sterilisation: highest success after Filshie clips, pregnancy rate 85%, ectopic rate <10%.
What is your approach to the management of an infertile couple with ENDOMETROSIS?
Mild-moderate disease:
- Surgery (laparoscopic excision of endometriosis and adhesiolysis) improves spontaneous conception rates.
Endometriomas:
- Refer for IVF.
- In conjunction with laparoscopic ovarian cystectomy (if >3 cm) improves conception rates.
Down-regulation for 3-6 months with GnRH agonist increases chance of pregnancy >4 x.
Controlled ovarian stimulation (COS) + IUI increases live birth rates 5-6 x.
What is your approach to the management of an infertile couple with UTERINE factor infertility?
- Lack of evidence of improved outcomes with treatment so decision to treat on individual basis.
Submucous fibroids: hysteroscopic resection.
Uterine septum: hysteroscopic resection.
Intrauterine adhesions: hysteroscopic division and insertion of copper IUD.
Intramural fibroids: myomectomy
What is your approach to the management of an infertile couple with UNEXPLAINED INFERTILITY?
Expectant management: 60% conceive within 3 years; more suitable if female <35 years old.
Controlled ovarian stimulation: clomiphene + timed sexual intercourse or IUI.
- Pregnancy rate 10-15% per cycle.
- Should have IVF if no success after three cycles.
For women with PCOS, the use of metformin alone results in ovulation with conception rates of ___%?
Up to 8%
Regarding COS + IUI:
What is the pregnancy rate (%) per cycle?
What is the cumulative pregnancy rate?
Pregnancy rate per cycle 10-15%.
Cumulative pregnancy rate 75%.
Describe the process of IVF:
- Induce development of several ovarian follicles with gonadotrophins.
- Prevent LH surge and ovulation of follicles by downregulating ovaries with GnRH agonist/antagonist.
- Follicle tracking (USS) until at least 3 follices >16 mm in size
- Given hCG trigger: causes oocytes to re-enter meiosis and expel the first polar body.
- 36-38 hours after trigger, TVUS guided needle aspiration of follicles; 90% yield an oocyte.
- Incubation of oocyte + sperm overnight; if fertilisation occurs embryos are incubated further.
- Embryo transfer 2 days after fertilisation under USS guidance; other embryos frozen and transferred later.
- Luteal support up to 8 weeks with vaginal progesterone (hCG injections have increased risk of OHSS).
List the indications for IVF treatment:
- Tubal factor: unable to have surgery or not conceived 6 month after surgery.
- Anovulation: not conceived despite ovulation induction.
- Unexplained: after 3 cycles of COS + IUI
- Endometriosis: moderate-severe.
- Male factor: moderate.
- Surrogacy
- Oocyte donation
- Donor insemination failure
List the prognostic factors for IVF treatment success:
- Shorter duration of infertility.
- First cycle of IVF
- Maternal age <35 years.
- Previous successful pregnancy (spontaneous or ART)
- BMI 19-30
- Non-smokers
- Salpingectomy if had hydrosalpinges.
Risk of HIV transmission and ART:
Where man is HIV positive, risk of transmission is negligible if all of the following criteria is fulfilled:
- Compliant with highly active antiretroviral therapy (HAART)
- Viral load <50 copies.mL for > 6 months.
- No other infections present.
- Unprotected sexual intercourse is limited to time of ovulation.
Risk of HIV transmission and ART:
What is the role of sperm washing when man is HIV positive?
Sperm washing reduces but does not eliminate risk of transmission.
Sperm washing decreases likelihood of success.
Risk of HIV transmission and ART:
Where man is Hep C positive, how would you counsel couple regarding risk of transmission with ART?
- Risk of transmission through unprotected sexual intercourse is low.
- However you would recommend eradication therapy before conception considered.
Describe the pharmacological effects on the hypothalamic-pituitary-ovarian axis which result in clomiphene citrate increasing ovulation. (4 marks)
- Anti-oestrogen / selective oestrogen receptor modulator
- Competitively inhibits oestrogen binding to its receptor.
- Primary site of action is at hypothalamus.
- Blocks negative feedback of circulating endogenous oestradiol leading to increased GnRH pulse frequency and increased serum concentrations of FSH and LH. This in turn increases ovarian follicular development.
- FSH stimulation of LH receptors in granulosa cells is enhanced.
Regarding clomiphene ovulation induction:
If ovulation/pregnancy not successful with initial 50 mg daily dose, what is your dosing regiment for 2nd and 3rd cycles and what is the max daily dose that can be given?
What is the maximum recommended number of cycles and why?
2nd cycle: 100 mg po daily.
3rd cycle: 150 mg po daily.
Max daily dose: 150 mg po daily.
Max number of cycles 12 due to increased risk of ovarian tumours.
What was the finding of the Cochrane Review (2019) looking at screening hysteroscopy in sub fertile women and women undergoing ART?
No high quality evidence to support the routine use of hysteroscopy in the general population of sub fertile women with a normal USS or HSG
In women undergoing IVF, low quality evidence suggests that performing a screening hysteroscopy before IVF may increase live birth and clinical pregnancy rates
What was the finding of the Cochrane Review looking at CC vs placebo for OI in PCOS?
CC improves the rates of clinical pregnancy
May be less likely to result in a live birth when compared with a gonadotrophin
What was the finding of the Cochrane Review looking at Metformin for OI in women with a diagnosis of PCOS and sub fertility?
(2019)
Metformin may be beneficial over placebo for live birth
But more women experience GI side effects
Uncertain if
- CC + MF > CC alone
- MF = or worse or better than CC
- effect of MF on miscarriage
What was the finding of the Cochrane Review of Gonadotrophins for OI in women with PCOS?
2019
In women with CC failure, gonadotrophins resulted in more live births than continued CC without increasing multiple pregnancies
What was the finding of the Cochrane Review of Laparoscopic Ovarian Drilling in women with PCOS?
2020
Lap ovarian drilling may
- decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical OI alone
- probably reduces number of multiple pregnancies
Insufficient evidence though
What was the finding of the Cochrane Review of IVF compared to other options for unexplained sub fertility?
2015
In women who were treatment naive
- no conclusive evidence of difference in live birth rates between IVF and IUI+gonadotrophins / CC
In women who had previously trialled IUI+CC
- IVF had higher live birth rate than IUI + gonadotrophins
IVF associated with higher live birth rates than expectant management
What is the karyotype in Kleinfelter’s Syndrome?
XXY
What is the incidence of Klinefelter’s Syndrome
1-2:1000
What is the only known risk factor for Klinefelter’s Syndrome?
Maternal age
Maternal age 40 - RR 4 c.f. Maternal age 24
What are the primary features of Klinefelter Syndrome?
Infertility
- primary hypogonadism with high FSH
- azoospermia
Small, non-functioning testes
What are symptoms of Klinefelter Syndrome?
Greater height Weaker muscles Gynaecomastia Less body hair Poor coordination
Normal intelligence
What is the definition of infertility?
The inability for a couple to conceive after 1 year of regular unprotected intercourse
What is the definition of fecundity?
The probability of conception over 1 menstrual cycle
When should laparoscopic ovarian drilling be considered?
PCOS
Only if good AMH
Only if high antral follicle count
Aim: to reduce the amount of androgen-producing tissue
