Subfertility Flashcards
Define infertility/subfertility
failure to conceive after:
12 months of regular unprotected intercourse (USI) <35yo
6 months in >35yo (WHO)
What is the epidemiology of subfertility
85% will become pregnant naturally within 1 year with regular USI , 92% will do so within the 2nd year cumulatively (93% third year)
1:7 couples struggle to conceive naturally
1 in 6 recognised pregnancies miscarry
What are the causes of subfertility
Ovulatory (F): 45%
Tubular (F): 25%
Male factors: 30%
Unexplained: 25%, usually failure of implantation
40% due to male and female factors
What is the normal length and blood loss of the menstrual cycle
Length: variable, 21-25 days in between normal
Average 35ml, >60ml = heavy
Describe the ovarian menstrual cycle
- Menstruation
- 5-13 (proliferative)
- Pulsatile GnRH release from the hypothalamus
- LH and FSH release → follicular growth
- Follicles secrete oestradiol and inhibin → negative feedback on FSH and LH release (prevents <1 follicle growth)
Oestradiol levels increase as the Graafian follicle emerges - day 14 (ovulation)
Oestradiol levels reach threshold to trigger a positive feedback response → LH surge (12h duration) → meiosis of the egg
The follicle ruptures and a mature egg is released 36 hours after the surge - 14-28 (luteal/secretory)
The remaining ruptured follicle becomes corpus luteum, which secreted progesterone
If fertilisation has not occurred, the corpus luteum degrades, so progesterone and oestradiol release also decreases
If fertilisation has occurred, the release of beta-hCG maintains progesterone release
Describe the endometrial menstrual cycle
- Menstruation
The endometrium breaks down and is shed - 5-13 (proliferative)
Oestrogen release allows for proliferative changes
Stromal cells proliferate
Glands elongate - day 14 (ovulation)
- 14-28 (luteal/secretory)
Progesterone release allows secretory changes
Glands swell
Blood supply increases
What is the role of AMH
AMH is produced from small ovarian follicles and reduces oestrogen release As the follicles grow, the production of AMH reduces and oestrogen levels increase
What are the important features to ascertain for the subfertility in women
See the male and female individually
- Age
- How long have they been trying for (+frequency, partner)
- Have they had a previous pregnancy (+outcome)
- Menstrual cycle - is bleeding regular
- Sexual history - is the sex regular? Unprotected? Vaginal? Penetrative? Ejaculatory? Any STIs?
What should you look for on examination for subfertility in women
General: BMI, hirsutism, acne
Breast: galactorrhoea
Abdo: ?mass, ?cyst
Pelvic: ?STIs, vaginismus
What are the important features to ascertain for the subfertility in men
Has he gotten anyone pregnant before
Any difficulties in sex
Occupation (affects time of sex)
Cannabis use
PMHx: mumps, STIs, testicular trauma/torsion
What investigations should be done for women with subfertility
LH (OTC urine kits) - Surge in LH can be detected the morning after it has occurred in the urine, rarely measured due to the small time frame (12h)
FSH (day2-3 of cycle)
Oestradiol (?ovulation)
Mid-luteal progesterone (7 days before predicted menstruation) - suggests ovulation (high)
AMH - ovarian reserve
Testosterone
SHBG
Prolactin
Pelvis USS
Hysterosalpingogram (HSG) - radio-opaque contrast injected through cervix, using X-ray
HyCoSy: Contrast injected, TVUSS used
Laparoscopy and dye test
What are the investigations for men with subfertility
Sperm:
1. Count - >15 mil per ml, 500,000 are required for a chance of fertilisation
2. Motility - 50% are motile, 25% are progressively motile, asthenospermia = not motile
3. Morphology - 4% have normal morphology
FSH
LH
Prolactin
Testosterone
TFTs
Karyotype (?Klinefelter’s)
Sweat test for CF
Testicular USS
What are the options for management in the following male factors contributing to subfertility: abnormal sperm, oligospermia, moderate-severe oligospermia, azoospermia
Abnormal: Optimise lifestyle factors, Examine scrotum
Oligospermia: Intrauterine insemination
Moderate-severe oligospermia: IVF ± ICSI
Azoospermia: Examine for presence of vas deferens, Check karyotype, CF, hormone profile, Surgical sperm retrieval → IVF + ICSI, Donor insemination
What are the ovulatory causes of subfertility in women
Hypog Hypog (hypothalamic)
- Stress/exercised-induced
- Anorexia nervosa
- Sheehan’s
- Pituitary tumours - adenoma or hyperplasia
- Kallman’s syndrome (GnRH-secreting neurones fail to develop)
Normogonadotrophic
- PCOS (80%)
Hypergonadotrophic
- Primary ovarian insufficiency
Hypo/hyperthryoidism
What is the management for subfertility due to PCOS
Lifestyle: weight loss, healthy diet, more exercise
First line: Clomiphene
± metformin (weight loss, ovulation)
Second line: Letrozole (aromatase inhibitor) = induces ovulation
Third line: gonadotrophic induction followed by HCG injection
Describe the use of clomiphene and what are the side effects
Blocks oestrogen receptors → increases FSH/LH release → endogenous oestrogen release
Given on day 2-6 of the cycle
Limited to 6 months use
Ovulation in 70%< live birth in 40%
Monitor with TVUSS in the first month to assess ovarian response
SE:
May cause thinning of the endometrium
Increased risk of multiple pregnancy
What is the management of Pituitary causes of subfertility in women
Kallman’s: exogenous gonadotrophins, GnRH pump
Pituitary cause: dopamine agonist e.g. bromocriptine, cabergoline
What are the tubal causes of subfertility
Infection/endometriosis
PID (Fitz-Hugh-Curtis): Adhesions within and around the fallopian tubes
Previous pelvic surgery: adhesions
Sterilisation -> IVF or open microsurgical tubal re-anastamosis (increased ectopic risk)
What is ovarian hyperstimulation syndrome and what are the risk factors
Gonadotropin overstimulates the follicles, which get large and painful.
Intravascularly deplete and third space fluid
More common in IVF than ovarian induction standalone
RF: <35yo, gonadotrophin stimulation, PCOS, low BMI
What are the symptoms of ovarian hyperstimulation syndrome
Pain
SOB (Pleural effusion)
Abdominal distension (Ascites)
Nausea and vomiting
Loss of appetite
Reduced urinary frequency/volume
What is the management for ovarian hyperstimulation syndrome
Expectant - keep patient stable and not intravascularly deplete
Consider clexane for increased VTE risk
Drain any ascitic fluid
What is the general management for subfertility
- Re-assure, inform on stats about conception
- Advise regular intercourse throughout the cycle (temp, charts, LH detection not recommended)
- Lifestyle advice:
- Use folic acid
- Rubella and cervical screening
- Stress management (affects libido)
- BMI 19-25
- Seek advice from occupational health at work
- Stop alcohol consumption - Refer to British infertility counselling association
Describe Intra-uterine insertion (procedure, live birth rate, contra-indications)
Sperm injected directly into the cavity of the uterus
5-10%
Tubes are not patent
Describe In-vitro fertilisation (procedure, live birth rate, contra-indications)
Embryo fertilised outside the uterus and transferred back
<36 = 35%
Ovarian failure
What is ICSI
Intracytoplasmic sperm injection
Injection of sperm into the oocyte cytoplasm
Used for male factor infertility
What are the options for assisted contraception
Intra-uterine insertion (IUI)
In-vitro fertilisation (IVF)
Intracytoplasmic sperm injection (ICSI)
Frozen embryo replacement (FER)
Oocyte donation
Preimplantation genetic diagnosis and screening (PGD/PGS)
Surrogacy
What are the indications for assisted conception
All other methods have failed
Unexplained subfertility
Male factor subfertility
Tubal blockage
Endometriosis
Genetic disorders
What are the complications of IVF
Superovulation: multiple pregnancy, ovarian hyperstimulation
Egg collection: intra-peritoneal haemorrhage and pelvic infection
Pregnancy complications: ectopic pregnancy, increased morbidity and mortality
Describe the IVF procedure
- Multiple follicular development
a. 2 weeks of daily SC gonadotrophin injections - Ovulation and egg collection
a. Drugs are stopped
b. Single HCG injection (or LH) to trigger final oocyte maturation
c. Egg collection 35-58h later - Fertilisation and culture
a. Until blastocyst stage
b. Can save spares for FER - Embryo transfer
Luteal phase support until 4-8 weeks (LH or HCG)
