Fertility Flashcards
What are the causes of female anovulatory infertility? (3) and an example for each
3 main causes
Anovulatory infertility:
Ovarian dysfunction
-80% PCOS - normal gonadotrophins
Hypergonadotrophin hypogonadism
Absence of ovarian hormones
- primary ovarian failure
- resistant ovarian syndrome - FSH receptor abnormalities
Hypogonadotrophic hypogonadism
Failure of the pituitary to produce FSH, loss of GnRH secretion
- primary eg stress anorexia exercise
-surgery, irradiation, inflammation (sarcoidosis or TB) sheehans, congenital eg kallmans
What are the categories for causes for female infertility?
Ovarian function
Tubal
Uterine
What are the causes for tubal damage resulting in infertility?
Infection
usually chlamydia
Also appendicitis, septic miscarriage, TB and other intransigence pathology can damage the tube
Endometriosis
Inflammatory response
What are the causes of uterine infertility
Intrauterine adhesions
Ashermanns
Endometriosis
Submucosal Fibroid if by tubal Ostia
Congenital defects eg bicornuate doesn’t affect fertility but later pregnancy complications
No difference in rate with fertile and jnfertile woman
Causes of male factor infertility (6) and examples
No cause in 50%
Primary testicular dysfunction
- failure of spermatogenesis eg trauma/ infection/ chemo
- microdeletions of Y
- chromosomal abnormalities eg kleinfelters
Obstructive
- congenital absence of the vas def 10% ( if bilateral consider CF)
- iatrogenic
- infective
Endocrine
- hypogonadotrophic hypogonadism
- hypoprolactinaemia causes impotence not reduction in sperm count
Drugs
- recreational eg EtOH marijuana and Tobacco affect function and production
- chemo causes irreversible azooaspermia
- ED for b blockers and antidepressants
- reversible affect on spermatogenesis : steroids, sulfasalazine, antifungal
Environmental
- occupational exposure to heat, radiation and chemicals
- ?? Something we don’t know about
Varicocoele
New evidence that antisperm antibodies do not effect infertility and should not be tested for
what is an Varicocoele and how does it affect infertility
It is a dilatation of the pampiniform plexus (L>R due to insertion of the spermatic vein into the renal vein.)
Surgical correction should be for symptoms - it does not improve sperm count
11% in fertile men and 25% rate in infertile men
UTD recommends repair if grade three, large with abnormal semen analysis
poor evidence either way
What pre - conception testing / optimisation should be done before fertility treatment is started
• Cervical screening
• Antenatal screen - blood group, ABs FBC
• Viral screen - HIV, Hep B and C
• TSH
• Immunity screen: Rubella and varicella
offered rubella immunisation if non immune and avoid pregnancy for 1 month
• Screen for chlamydia before the uterus is instrumented (if positive, manage) - consider prophylactic antibiotics if not
• HbA1c if obese with PCOS
Weight loss, smoking cessation, manage EtOH
Folic acid for prevention of NTD 0.4mg daily. If prev NTD, on antiepileptic or diabetic then 5mg
- preconception up to 12 weeks
What is the clomiphine citrate challenge test
Clomiphine citrate challenge test - 100mg clomiphine day 5-9
Why when testing for ovarian reserve D3 FSH and estradiol
Measure D3 estradiol and FSH and D10 FSH
- lower reserve means higher FSH early in the cycle as the follicles of the ovary are not secreting enough hormone to suppress it
High D3 estradiol are due to advanced premature follicle recruitment that occurs in woman with poor ovarian reserve
Normal woman have enough hormone from small follciles in early cycle to suppress FSH - if this is high there are not enough early cycle follicles so FSH is high
high estradiol can falsely suppress FSH so if you just do FSH then you can be falsely reassured so must test both
Lifestyle advice for fertility
For men drinking 3-4 units / day is unlikely to affect their semen quality - Excessive alcohol is detrimental to semen quality
Smoking reduces fertility in M+W - + lifelong heath
No evidence with the relationship between caffeinated beverages and fertilty
High BMI (over 30) likely to take longer to conceive
If BMI over 30 and not ovulating weight loss will help
Group programmes with dietary and lifestyle advice are more successful then weight loss advice on its own
Men with BMI over 30 likely have reduced fertility
Woman with BMI under 19 and have irregular menstruation - it is likely that gaining weight will improve conception
Elevated scrotal temperature reduces semen quality but no evidence on wearing tight underwear
Screen for occupational exposure
OTC and recreational drug use can affect fertility
Complementary therapies are not evidenced based and not investigation is needed before the intervention can be recommended
Why does endometriosis cause infertility?
Local inflammatory state
endometriotic nodules secrete estradiol and progesterone that attracts macrophages, VEGF, IL 8 and cytokines
This is toxic to the gametes
Induced progesterone resistance
Impairing oocyte release
increased apoptosis of granulosa cells
Derranged follicular enviroment
Adhesions prevent oocyte release
Reducing sperm and embryo transport
Peritoneal macrophages phagocytose sperm
local inflammation impairs implantation
What is the rate of endo in fertile woman?
Infertile woman?
In woman with subfertility 50% have endometriosis
In fertile woman 5-10% have endo
In woman with endo 2-10% fecundity rate (compared with fertile couples 15-20%)
how does lipidol affect pregnancy rates ?
how long does that last for?
RCT showing tubal flushing with lipiodol increases pregnancy rates at 6 months, not at 2 years RR 4.4 48 vs 10%
What are the reasons to and not to resect endometriomas for infertility management
Exclude malignancy (1 extra ovarian cancer for every 10 000 woman with endometriosis – increased risk from 1/100 to 2/100)
Relieve symptoms
Reduce the risk of cyst complications (rare)
Facilitate transvaginal access to follciles
Risks
Reduced the number of oocytes able to be retrieved
Reduces peak oestradiol levels
Increased FSH requirement
In 13% of cases it leads to ovarian failure in that ovary
Surgical risk
May not benefit pregnancy rates
What are the indications for myomectomy in an infertile woman?
Indications for myomectomy in infertile woman
Fibroid size, number and location may impact on utility of myomectomy
Infertile woman / woman undergoing ART with submucosal fibroids
Infertile woman with symptomatic fibroids – HMB / pressure sx
Couples with multiple failed ART cycles with IM fibroids
what is the success rate of clomiphine ?
how does it work?
PCOS - 80% ovulation 30-40% pregnancy in 6/12
Bind to oestrogen receptors and have mixed agonist and antagonist activity
Primary site hypothalamus- blocking E receptors and negative feedback of E so increase in pulsatile GnRH and therefore FSH and LH. Likely also pituitary action.
In the ovary in a low E state it acts as an agonist enhancing FSH stimulation in the granulosa cell
Anti estrogen in the uterus cx and this may drop overall pregnancy rate - don’t get same build up of endometrium
What are risks of clomiphine?
Twin 7-9% Triplet 0.3%
Hot flashes, breast discomfort, abdo pain and distension
OHSS rare
Visual symptoms like double or blurry vision – indication to stop treatment
Can cause luteal phase defect
What lifestyle choices affect IVF success
Caffeine consumption has an adverse effect on outcome
BMI 19-29 - reduces success outside this
Smoking by either parent has a negative outcome of success
Alcohol more then 1 unit / day reduces the effectiveness of ART
When is donor sperm indicated?
Donor insemination is used in situations where a male partner is infertile or in same-sex couples. However, the indications expanded such that it has become an alternative approach to fertility for some couples.
Donor insemination can also be considered in:
Couples in whom one or both partners are carriers of a heritable disease.
Couples who are serodiscordant for sexually transmissible viral infections.
Women without a male partner.
Couples who are incompatible for red cell antigens (e.g., D, Kell) associated with haemolytic disease of the newborn and with a history of a severely affected infant.
What is the incidence of OHSS with IVF?
Mild ovarian hyperstimulation syndrome occurs in 33% of ART cycles, with severe OHSS occurring in 3.1–8.0% of cycles.
What are the OHSS risk factors?
young age
polycystic ovarian disease
diabetes
previous OHSS
high follicular phase LH
high-dose gonadotrophin stimulation regimens
the use of GnRH analogues as opposed to GnRH antagonists
multiple follicular response with stimulation
high serum estradiol levels during treatment (>20 000 p/mol)
exposure to hCG, as trigger or luteal support
conception (increased in multiple pregnancy).
How do reduce OHSS risk?
using low-dose stimulation protocols, or natural-cycle IVF
follicular monitoring
utilising GnRH antagonist cycles rather than GnRH analogues
utilising progesterone instead of hCG for luteal suppot
abandoning ART cycles prior to hCG administration and oocyte collection
delaying embryo transfer following collection and elective freezing of all embryos
coasting, whereby the hCG trigger is withheld until serum estradiol levels have returned to acceptable levels
GnRH agonist triggering the final maturation of oocytes, but pregnancy rates are reduced.
What are early pregnancy complications in IVF?
0.7% ectopic
1/100 heterotopic
Spont loss 25%
twin loss 35% triplet 55%
IVF AN risks ?
showed significantly increased rates of perinatal mortality, preterm delivery, low birth weight and neonatal intensive care unit admissions, placenta praevia, gestational diabetes and pre-eclampsia for IVF pregnancies.
