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)
Tubal patency
Disease can be proximal (25%) or distal (75%)
PID 2ry to chlamydia is the commonest cause of tubal damage
Risk of tubal damage is about
12% after one episode of pelvic infection,
23% after two episodes, and
54% after three episodes
Other causes: septic abortion, ruptured appendix, pelvic surgery and ectopic pregnancy
Tubal patency examinations
Hysterosalpingogram (HSG)
Hysterosalpingo-contrast-ultrasonography (HyCoSy)
Laparoscopy & dye
If low risk of tubal disease offer HSG or HyCoSy
Chlamydia screening before instrumentation (because injecting dye pushes chlamydia further up cervix into fallopian tubes)
HSG
Done 2-5 days after menstruation
Antibiotics should be given to prevent the flare-up of infection if H/O PID
The overall risk of infection is approximately 1%
In high-risk population this can rise to 3%
HSG vs laproscapy and dye
HSG Advantages:
relative safety
ease of use
delineation of the uterine cavity and Fallopian tubes
HSG Disadvatages:
Inability to assess the pelvic peritoneum
Ideal screening test for the majority of the patients
HyCoSy (ultrasound and dye)
Similar to HSG
No radiation -> Relatively safer
Ovarian and uterine assessment is possible
Time-consuming & requires training
Laproscopy & dye advantages and disadvantages
Invasive procedure with inherent risks of visceral injury to the patient
Lap & dye is more sensitive & specific
Chance to diagnose & treat endometriosis & adhesions
Uterine abnormality
Adhesions, polyps, submucous fibroids and septae, are estimated to be a factor in 10–15% of couples seeking treatment
HSG, TVS & hysteroscopy
Hysteroscopy is undoubtedly better than HSG & TVS at detecting these abnormalities
Ovulation induction
Clomid (Clomifene Citrate) for women who have PCO
Anti-oestrogen effect on hypothalamic pituitary axis
FSH injections for resistant PCO or Hypogonadotrophic Hypogonadism
Risk of multiple pregnancy
Monitor 1st cycle using USS
IUI treatment indications
Unexplained
Mild male factor
Mild endometriosis
IUI advantages
LESS STRESS
LESS INVASIVE
LESS TECH
CHEAP
IUI treatment
Inject pure sperm (not semen) to the top of the uterus near the egg
0.25ml
Success rate - 10% per cycle
NICE guidelines for IUI treatment
Do not offer IUI for couples who have unexplained infertility
IUI for single women, same sex couple or heterosexual couple who have problem with intercourse
IVF for couples who have unexplained infertility
IVF indications
Tubal damage
Low sperm quality
Unexplained infertility
Low ovarian reserve
Function of fallopian tubes
narrow ducts located in the human female abdominal cavity that transport male sperm cells to the egg, provide a suitable environment for fertilization, and transport the egg from the ovary, where it is produced, to the central channel (lumen) of the uterus
What is ICSI?
(intra-cytoplasmic sperm injection)
For men with very low sperm counts or no sperm in the ejaculate
Do surgical sperm retrieval from testis or epididymis and inject into the egg
Higher risk of chromosomal abnormalities - not sure if due to process or due to higher chance of abnormalities in men with lack of sperm/low sperm count
Embryo development/transfer
Most common is day 5 transfer as this is the physiological stage of embryo transfer and the egg will be more synced with the endometrium.
Injected into top of uterus to implant in the endometrium
IVF LBR
Depends on female partner’s age
Varies from one unit to another
National average 30-35% < 35 year old
