Subfertility and assisted Conception Flashcards
Definition of fecundity
The chance of conception for a couple over 1 month
Average fecundity for a couple under 32 y/o
20% per month
Statistics for rates of natural conception
20% of couples will conceive within 1 month
80% within 1 year
86% within 2 years
90% within 3 years
When do you begin to investigate subfertility
In all couples after 1 year of failing to conceive
Earlier should be offered to higher risk couples:
- women older than 35y
- history suggestive of anovulation, tubal disease or male factor problems
How common are male factor problems in fertility, what is the main cause
5% of men are subfertile
85% of these have suboptimal semen quality
Topics of causes of infertility
Oocytes: ovulation, ovarian reserve, timing of sexual intercourse Tubal factors (patency) Other female factors: abnormal uterine anatomy Male factors: suboptimal sperm, azoospermia, coital dysfunction, immune factors
Causes for anovulation/impaired ovulation
HPO axis disruption:
- BMI higher than 29 or less than 19
- PCOS (most common cause)
- Hyper- or hypothryroidism
- Hyperprolactinaemia
Cycle of ovulation
Primordial follicles - Pre-antral (primary) follicles - secondary follicles (oocyte + granulosa cells) - antral follicles (zonal pellucida) - dominant follicle - Ovulation - Corpus luteum development
Spermatogenesis cycle
Begins at puberty and continues throughout life
74 days to produce sperm
10 days to travel to head of epididymis
70% of mature sperm stored in head
Ejaculation - passage of sperm through vas deferens into urethra adjacent to prostate
7 day lifespan in uterus
What is azoospermia
Absence of MOTILE sperm in semen
Causes of fallopian tube obstruction
Previous pelvic inflammatory disease (e.g. chlamydia)
As a result of any inflammatory process in abdomen/pelvis ( surgery, endometriosis, IBD - all cause adhesions)
Causes of unsuccessful implantation
Abnormal endometrium:
- Fibroids
- Uterine adhesions (Asherman’s syndrome)
- Uterine polyps
Cycle of oocytes in female lifetime
highest number in 2nd trimester of pregnancy in a female foetus
Sharp decrease during third trimester
Progressive decline in number of oocytes after birth
Complete depletion at menopause
Pre-conception advice
Stop smoking Moderate alcohol (no binges) Avoid drugs (especially cones) Moderate exercise Optimise BMI Avoid occupational exposures Female: folic acid, vitamin B6 & B12, omega 3 Males: Vitamin E, selenium
Optimal timing of intercourse for conception
few days before ovulation to a few days after (ovulation always occurs 14 days before start of period)
How to tell when ovulating
Clear endocervical mucous (spinbarket - stringy and pliable)
Ferning on slide
Basal body temperature rises
Investigations of ovulation
Day 21 progesterone - rises in response to ovulation
Basal body temperature - rises in response to progesterone
LH kits - detect LH surge prior to ovulation
Cycle tracking - measure of oestrogen, progesterone and LH throughout cycle, performed by fertility specialist, can determine when ovulation has occurred
Investigating ovarian reserve
Relatively new, specialist test
“Egg timer test”
- perform on day 3-5 of cycle
- FSH, AMH and US of ovarian volume and antral follicle count
high FSH and low AMH indicates low reserve
Age-based test - compare to likely parameters at that age
History required when assessing sperm-related factors of subfertility
Fathered other pregnancies
Congenital issues (e.g. cryptorchidism)
Previous surgery/trauma/hernias/torsion
Infections (mumps orchitis, STIs - obstructed vas)
Other illnesses (cancer, CTx, CF)
Smoking, drinking, drugs
Occupational exposures (Solvents, radiation, mining chemicals)
When to perform semen analysis
3-4 days after sexual abstinence
2 abnormal results required to diagnose male subfertility
Normal parameters for semen analysis
Volume more than 2mL pH more than 7.2 Sperm conc more than 20M/mL total sperm count more than 40M/ejaculate Motility more than 50% grade a and b Morphology more than 30% normal forms
Tests indicated if low sperm count or azoospermia
testosterone levels
LH and FSH
screen for CF gene (congenital bilateral absence of vas deferens)
Most common causes for subfertility and how common are they
Ovulatory dysfunction 30% Tubal Pathology 15% Male factor 20% Unknown cause 20% Endometriosis 7% Uterine causes 3% Cervical causes 2% Multiple causes 3%
How common is subfertility
Affects 1 in 7 couples
Assessing tubal patency in a patient with a low-risk history
Hysterosalpingogram - dye inserted into womb, watch its passage through tubes (reliable indicator of patency, not obstruction)
Saline hysterosalpingography - put ultrasound dye into womb and watch passage in tubes
Assessing tubal patency in a woman with a high-risk history
Laparoscopy + dye
Assessing a woman for congenital uterine anomalies
Best assessed by laparoscopy + hysteroscopy, saline hysterosalpingography or 3D ultrasound
Assessing a male’s sexual function
How often do you make love? Do you get erections? Can you penetrate partner deeply? Do you reach an orgasm? Do you ejaculate?
Step-wise approach of assisted conception
- ovulation induction
(clomifene citrate, laparoscopy ovarian drilling if polycystic, small dose FSH) - Intrauterine insemination
- IVF/ICSI
Outcome of clomifene citrate
70% of women will ovulate
Pregnancy rate of 10-15%
10% risk of pregnancy being multiple
Mechanism of action of clomifene citrate
Blocks oestrogen receptors in hypothalamus - blocks negative feedback response - induces increased production of gonadotrophin releasing hormone - increased production of FSH - increased follicle production in ovaries - increased ovulation
Indications for intrauterine insemination
Unexplained subfertility
Anovulation unresponsive to ovulation induction
Mild male factor
Minimal to mild endometriosis
Intrauterine insemination procedure
Introduction of small sample of prepared sperm (from ejaculate, surgical retrieval, or donor sperm) into uterine cavity with fine uterine catheter
+ mild stimulation with FSH to produce mature follicles
Follicular tracking to avoid over or under stimulation
Success rate of intrauterine insemination
15-20% success rate
Indications for intrauterine insemination with donor sperm
Azoospermia
Single women
Same sex couples
Management for women with low ovarian reserve
Prompt referral to specialist for fertility advice
Associations of low ovarian reserve
Poor response to gonadotrophins (main form of fertility therapy)
Poor oocyte and embryo quality
Increased miscarriage rate
Management options of subfertility in women with tubal pathology
Surgery - if pathology amenable to repair
In vitro fertilisation
Indications for in vitro fertilisation
tubal pathology
Patients with no success following ovulation induction, intrauterine insemination and donor insemination
Donor egg indications
Women with poor egg quality:
- older women
- premature ovarian failure
Previous surgery/chemo/radiotherapy which adversely affected ovarian function
Success rate of IVF
in women under 35y - 30% success rate per cycle
Procedure in IVF
- Ovaries stimulated with FSH (aim for 8-10 follicles)
and Monitor for apporx 2 weeks - Inject hCG to induce ovulation
- Collect eggs with US guided fine needle
- Fertilisation of eggs in petri dish (or intracytoplasmic sperm injection if required)
- Fertilised embryos replaced into uterine cavity
- Pregnancy test performed 2 weeks later
Risks of IVF
Higher rate of ectopic pregnancies (3-4%)
Overstimulation of the ovaries (ovarian hyperstimulation syndrome)
Ovarian hyperstimulation syndrome: cause and presentation
Iatrogenic due to increased FSH - increased follices - increased VEGF - increased capillary permeability
Ascites, hugely enlarged multi-follicular ovaries (painful), pulmonary oedema, multi-organ failure, coagulopathy
Management options for male factor subfertility
FSH and hCG injections if primary hypogonadism
Intracytoplasmic sperm injection (present but low quality sperm)
Surgical sperm retrieval (if absence of naturally ejaculated sperm)
Procedure of surgical sperm retrieval
Fine needle inserted into epididymis or testicular tissue to obtain sperm or testicular tissue with sperm respectively
Retrieved sperm can be cryopreserved or injected into the oocyte as a fresh IVF/ICSI cycle
Pregnancy rate for thawed gametes following cryopreservation
Almost that of non-cryopreserved IVF
Percentage of women with PCOS who have subfertility
75%
Return to normal ovulation after ceasing OCP
Many women will return to normal menses and fertility within 30 days
All women should return to normal menses and fertility within 90 days
Return to normal ovulation after removing an implanon
Levels of circulating etonogestrel undetectable within 1 week
Over 90% of women will ovulate within 3-4 weeks of removal
Diagnostic criteria for PCOS
Rotterdam criteria (requires 2 out of 3)
- oligo and/or amenorrheoa
- Clinical and/or biochemical evidence of hyperandrogenism (raised FAI or free testosterone)
- Polycystic ovaries on USS (8+ subcapsular follicular cysts under 10mm in diameter)
+ exclusion of conditions that may mimic PCOS (thyroid, CAH, prolactin etc.)
