14) Subfertility - Overview & ART Flashcards
Definition of subfertility
Unwanted delay in conception after 1 year of regular unprotected intercourse (or 6 cycles of IUI)
Incidence of subfertility
15%
What are the overall outcomes for subfertile couples?
15% subfertile.
50% of these will conceive spontaneously (or with simple advice).
8% remain sub fertile and require more complex treatment (4% primary, 4% secondary).
Only 4% of population remain involuntarily childless.
What is the rate of conception in the first month of trying and what is the monthly conception rate after 1 year?
Most likely to conceive in first month - 15-20% conception rate.
After 1 year, 5% per cycle.
In an unselected population, what percentage of couples will have conceived after 6 months, 1 year, 2 years?
6 months: 60%
12 months: 85%
24 months: 95%
In a woman aged 19-26 what is her 1 year and 2 year chance of conception, compared to a woman 35-39 years?
19-26: 1 year 92%, 2 years 98%.
35-39: 1 year 82%, 2 years 90%.
What proportion of women in their 40s are able to conceive?
50%
When during the menstrual cycle is conception most likely to occur?
Probability rises from 6d pre-ovulation, peaks 2d pre-ovulation and falls by the day of ovulation.
What are the incidences of the different causes of subfertility?
40% - both male and female component 30% - male factor 25% - ovulation disorders 25% - unexplained 20% - tubal damage 5-10% - endometriosis
How to investigate a sub fertile couple?
1) Sperm analysis
2) D21 progesterone
3) Assessment of tubal function
For how long should a man be abstinent prior to sperm sample?
2-3 days
What is the normal value for sperm volume?
> 1.5mL
What is the normal value for sperm pH?
> 7.2
What is the normal value for sperm concentration?
> 15million/mL
What is the normal value for sperm number?
> 39 million
What is the normal value for sperm motility?
> 40% (>32% progressive)
What is the normal value for sperm vitality?
> 58%
What is the normal value for sperm morphology?
> 4%
What to do if the sperm sample is abnormal?
Repeat in 3 months (or if grossly abnormal repeat ASAP)
Options for assessment of tubal function
HSG (if not known to have co-morbidities)
HyCoSy (ultrasound) is an alternative to HSG
Lap + dye if thought co-morbidities
When to test thyroid in sub fertility patients?
If symptomatic
When to test prolactin in fertility patients?
If ovulatory disorder, galactorrhea or pituitary tumour
When to test FSH/LH in fertility patients?
Irregular menstrual cycles
What tests are used to predict likely ovarian response to gonadotrophin stimulation in IVF?
Total antral follicle count (done on D2-D5 via TVUS)
- low response <4, high response >16.
AMH - low response <5.4, high response >25
FSH (D2-D5 of cycle) - low response >8.9, high response <4
Who are the legal parents of a child born through fertility treatment?
- Heterosexual couple using their own gametes - both parents irrespective of marital status.
- Sperm donor used - if married/CP then both parents, if not married/CP then need to fill out a form before treatment.
- Egg donor used - both parents (birth mother is legal mother)
- Surrogacy - birth mother and her husband/CP are the legal parents. Parental order can only be issued after birth for commissioning couple to assume parental role.
When can a child born via donor games access information about donor?
Non-identifying information age 16.
Identifying information age 18.
What is meant by oligo(zoo)spermia?
Reduced concentration of sperm
What is meant by astheno(zoo)spermia?
Reduced motility of sperm
What is meant by terato(zoo)spermia?
Reduced normality of sperm
What is meant by azoospermia?
No sperm in ejaculate
What is meant by aspermia?
No ejaculate
What is meant by necrozoospermia?
Only dead sperm
What is meant by globozoospermia?
Acrosome completely absent from sperm
What is the most common abnormality on semen analysis?
Oligo-terato-asthnospermia (OAT) - unexplained!
Management of male subfertility
Hypogonadotrophic hypogonadism - gonadotrophin drugs
Obstructive azoospermia - surgical correction
Treatment of ejaculatory failure
Assisted reproductive techniques e.g. ICSI/donor
What to do about leucocytes in semen?
Nothing unless infection identified
What to do about varicocele?
Don’t offer surgery - doesn’t improve pregnancy rates
How to confirm anovulation?
Clinically: If woman is oligomenorrhoeac (cycle 6w –> 6m) or amenorrhoea (no natural period >6m)
If regular cycles - D21 progesterone (>30 confirms ovulation, >15 suggestive)
What is type 1 ovulatory disorder and what percentage of ovulatory disorders does it account for?
Hypothalamic pituitary failure (hypogonadotrophic hypogonadism) - 10%
What is type 2 ovulatory disorder and what percentage of ovulatory disorders does it account for?
HPO dysfunction (predominantly PCOS) - 85%
What is type 3 ovulatory disorder and what percentage of ovulatory disorders does it account for?
Ovarian failure (hypergonadotrophic hypogonadism) - 5%
Treatment of type 1 ovulatory disorder
- Increase BMI if <19 and moderate exercise.
- Pulsatile GnRH (or gonadotrophin with LH activity) will induce ovulation in 95%
- If due to prolactin, address underlying cause +/- bromocriptine
Treatment of type 2 ovulatory disorder
- Weight loss if BMI >30
- Pharmacological: Clomifene, metformin, Combination of both
- Second line treatments: Laparoscopic ovarian drilling, combined clomifene/metformin, gonadotrophin (FSH only, unlike patients with Type 1 ovulatory disorder)
What monitoring should be done during clomifene treatment?
Ultrasound monitoring during first cycle - if >2 mature follicles recruited avoid unprotected intercourse.
Serum progesterone D21 to ensure ovulation and increase dose if not.
When should clomifene be given?
For 5 days from D2/D3.
Not for more than 6 months.
When does ovulation after clomifene occur?
7 days after last dose
What percentage of patients have uterine factors identified?
10-15%
What is the gold standard investigation for uterine factors?
Hysteroscopy
Data on polyps and fertility
Limited
Data on fibroids and fertility
Cause subfertility and pregnancy rates improve after myomectomy
What to do with intrauterine adhesions?
Offer adhesiolysis
Congenital anomalies on subfertility
Unclear
Sensitivity of HSG for detecting tubal pathology
50%
When should HSG be done?
10 days of LMP (after excluding chlamydia infection)
Treatment for women with tubal factors
IVF first line for moderate/severe/bilateral tubal disease.
Hydrosalpinges should be offered salpingectomy before IVF (as they reduce the success rate 50%)
Proximal tubal obstruction can be offered tubal catheterisation/hysteroscopic cannulation.
(For women with mild tubal disease, tubal surgery more effective than no treatment)
Average cycle fecundity for women with unexplained fertility without treatment
1.3-4.1%
Treatment for women with unexplained fertility
Try to conceive for 2 years –> IVF
Don’t offer ovarian stimulation
When can IUI be done?
Can be done in natural cycle or stimulated cycle.
How is the cycle stimulated for IUI if a stimulated cycle is performed?
5 days of clomifene or 7-10d gonadotrophin.
When 1-3 suitably sized follicles with 1 dominant follicle >17mm then injection of hCG is given.
Insemination of sperm 24-36h after hCG.
What does NICE say should be offered on NHS for IVF?
Age < 40 (not conceived after 2 y of intercourse or 12 cycles insemination) - 3 full cycles (where each cycle is 1 episode of ovarian stimulation and transfer of any resultant embryos).
Age 40-42 - 1 full cycle.
What are the two protocols involved in IVF stimulation?
“Long” (agonist) protocol:
- GnRH agonist (buserelin/noferelin) for 2-3w to desensitise pituitary
- Ovarian stimulation with gonadotrophin (hMG/rFSH) until desired follicular response obtained
- hCG for final maturation
- Oocyte collection 34-37h after final hCG
“Short” (antagonist) protocol:
- No downregulation stage
- Gonadotrophin (hMG/rFSH) administered in early menstrual phase (D2/D3)
- GnRH antagonists from D5/6 (prevent premature leutinisation)
- hCG to induce final maturation
- Oocyte collection 34-37h after final hCG
Which IVF stimulation protocol has higher rates of OHSS and shouldn’t be used in PCSO?
Long/agonist protocol.
How many embryos should be transferred?
For women <37 years:
- First full cycle - SET
- 2nd full cycle - SET if >1 top-quality embryos, 2 if no top-quality embryos
- 3rd full cycle - No more than 2
For women 37-39 years:
- 1st & 2nd full cycle - SET if >1 top-quality embryos, 2 if no top-quality embryos
- 3rd full cycle - No more than 2
40-42 years: Consider 2 embryos
What is given for luteal phase support?
Progesterone until 8 weeks
What is the birth rate per embryo transferred?
21.4%
What percentage of overall births is ART responsible for?
2.1%
What is the role of kisspeptin + GIH/RFRP?
Modulate GnRH release
What modulates LH/FSH release?
Sex steroids, inhibin, prolactin, activin, follistatin
What is the effect of FSH in the ovary and in the testes?
IN the ovary it acts on granulose cells to promote aromatisation of androgens to estrogens.
In the testes it acts on sertoli cells to increase sperm production.
What is the effect of LH in the ovary and in the testes?
In the ovary it acts on the theca cells to produce androgen.
In the testes it acts on the leydig cells to produce testosterone.
What is the role of pre-treatment before ART?
Doesn’t affect chance of live birth.
Can use in women on antagonist protocol to schedule IVF.
Pretreatment with GnRH analogues for 3-6 months in women with endometriosis associated sub fertility increases odds of clinical pregnancy 4x.
What is the difference between agonist and antagonist protocol outcomes?
Reduced follicles/oocytes with antagonist protocol but no difference in live birth rate.
Reduced OHSS with antagonist.
What is the purpose of the pituitary downregulation (agonist/antagonist)?
To suppress endogenous LH/FSH and premature ovulation.
What is the purpose of the gonadotrophin phase?
To achieve multi follicular development
What is the purpose of the final trigger?
Achieve follicular maturation
What is the first line final trigger substance?
Urinary hCG
How to obtain sperm samples?
Ideally by masturbation after 2-5d abstinence.
If retrograde ejaculation then can do urine samples post-masturbation.
Surgical methods if required.
Appropriate surgical sperm retrieval techniques for someone with obstructive azoospermia.
Percutaneous or microsurgical epididymal sperm aspiration.
Testicular sperm aspiration.
Appropriate surgical sperm retrieval techniques for someone with non-obstructive azoospermia
Microscopic testicular sperm extraction or open testicular biopsy.
Best predictor of ART success
Female age
How does obstetric history predict ART success?
Spontaneous pregnancy 20% increased success rate.
Prev ART pregnancy 60% increased success rate.
Effect of BMI on ART success?
None! But obstetric risks increased therefore get BMI <30
