7. Causes and treatments of subfertility Flashcards
What are the requirements for conception?
Progressively motile normal sperm capable of reaching and fertilizing the oocyte.
Timely release of a competent oocyte.
Free passage for the sperm to reach the oocyte and for the embryo to reach the uterus.
A mature endometrium that allows implantation.
What is infertility?
Inability to conceive after 2 year of frequent unprotected intercourse
Cumulative probability of pregnancy is 84%, 92% & 93% after 1,2 & 3 years
Reasonable to investigate after 1 year unless there is a concern
Infertility definition
Infertility definition:
“The period of time people have been trying to conceive without success after which formal investigation is justified and possible treatment implemented”
If a woman has not conceived after a year, offer further clinical assessment and investigation, along with her partner
Causes of infertility
1 in 6 couples will have a problem conceiving
Causes:
Unexplained 30%
Ovulatory 27%
Male factor 19% (has increased to 25-30%)
Tubal 14%
Endometriosis 5%
Other factors 5% (uterine, endometrial, gamete or embryo defect)
Combined male & female in 39%
Indications for early referral/investigations for females
Aged over 35 years Amenorrhoea/oligomenorrhoea Previous abdominal/pelvic surgery Previous PID/STD Abnormal pelvic examination
Indications for early referral/investigations in males
Previous genital pathology (history of testicular maldescent, surgery, infection or trauma, there is a greater incidence of abnormal semen parameters)
Previous STD
Significant systemic illness
Abnormal genital examination
Semen analysis requirements
Count > 15 x 106 / ml
Motility > 40%
Morphology > 4%
Volume 1.5-6 mls
Abnormal sperm analysis
No reason in 50%
1ry testicular failure is the commonest cause for oligo/azoospermia
Obstructive or non-obstructive azoospermia -> FSH, LH & T
Y chromosome microdeletion & cystic fibrosis if sperm count < 5 million
Female’s age is the single most important factor
A woman’s fertility declines with age
This is due to the decline in oocyte number and quality rather than uterine receptivity
The increased rate of chromosomal abnormalities in the oocyte also results in higher aneuploidy and miscarriage rates
Female assessment
Screen for chlamydia & Rubella
Ovarian reserve Early follicular phase hormone level (FSH, LH & E2) AMH (Anti-Mullarian Hormone) AFC (Antral Follicle Count) AMH and AFC go up
Ovulation test
Tubal test
AMH in males
In the male human production of AMH, by the sertoli cells, is initially high, yielding circulating concentrations in excess of 50 ng/ml (350 pmol/L) in early life. It declines at reproductive maturity under the influence of testosterone and FSH.
AMH in females
In the female AMH is first produced by the granulosa cells of the early growing follicle (preantral and small antral stages – when <4mm), and it continues to be produced by the granulosa cells of growing follicles up until the early antral stage whereupon it declines precipitously – once they reach 8mm in diameter by this time almost no AMH is made.
This is central to its value in reflecting the size of the number of small growing follicles and thus, by implication, the number of primordial follicles.
Levels remain fairly constant (and during menstrual cycle) so it can be a useful measure of ovarian reserve.
Circulating AMH may accurately reflect the total developing follicular cohort - which may represent the total ovarian reserve.
AMH
Produced by the Granulosa cells of pre-antral and small antral stages
Levels of AMH constant through monthly periods but declines with age
Higher AMH levels predict a good response
Lower AMH levels predict a poor response
Ovulation
Most women who have a regular menstrual cycles (26–35 days) will be ovulating
BBT (base body temp), Ovulation detection kits, cervical mucous pattern, follicular tracking or mid-luteal phase P4 (7/7 before menstruation)
Mid-luteal P4 >30nmol/L -> accepted as evidence of ovulation
?? Leutinised unruptured follicle
Follicular tracking is more reliable but costly & labour intensive
Ovulation problems
PCOS commonest cause of anovulation and 1ry or 2ry oligo/amenorrhea
If oligo/amenorrhea -> FSH/LH, E2, prolactin, TFT, androgens & SHBG
85% -> PCO (normal FSH/LH & E2)
5% -> POF (high FSH & low E2)
10% -> hypogonadotrophic hypogonadism (low FSH & low E2)