Define subfertility
Failure to conceive after one year of regular unprotected intercourse
What is the incidence of subfertility?
15%
What aspects should you ask about in the history of the male partner?
HxPC:
- Length of time trying
- Any symptoms of erectile dysfunction
- Ix or Tx so far
- Any child from previous relationship
PMed/Surg:
- Undescended testes
- Mumps orchitis
- Cancer
Sexual Hx:
1. Previous STIs
Social Hx:
- Occupation
- Alcohol
- Drug use
What aspects should you ask about in the history of the female partner?
HxPC:
- How long trying
- What Ix and Tx so far
- Menarche, periods - duration, cycle, menstrual diary
- Are they timing intercourse around ovulation
PMed Hx:
- Chronic conditions
- Thyroid
- DM
P Gynae Hx:
- STIs
- PID
- PCOS
- Gynae conditions
P Obs Hx:
1. Past pregnancies if any
Medications:
- Folic acid
- Other meds
Social Hx:
- Smoking
- Alcohol
- Drug use
- Occupation
What would you look for on examination in the male partner?
- General medical examination
- Height - Klinefelter’s syndrome (taller)
- Inguinal scars
- Size/site of testes
- Varicocoele/epididymal cyst
What would you look for on examination in the female partner?
- General:
- exophthalmos
- anaemia
- goitre
- hirsutism
- BMI - Pelvic examination:
- Masses
- Cx smear
List the causes of subfertility
- Anovulation
- Male factor
- No fertilisation
- Unexplained
List the causes of anovulation
- PCOS
- Hypogonadism
- Hyperprolactinaemia
- Thyroid dysfunction
- Ovarian failure
*30% of subfertility
List the causes of male factor subfertility
- Idiopathic
- Varicocoele
- Antibodies
- Drugs/chemical exposure
*25% of subfertility
List the causes of no fertilisation
- Tubal damage:
- Infection
- Surgery
- Endometriosis - Cervical <5%
- Sexual factor 5%
What percentage of subfertility is unexplained?
30%
What investigations would you do for subfertility in the female?
BLOODS:
- D21 progesterone >30nmol/L (to confirm ovulation) (taken 7days before the subsequent menstruation so may not be D21 depending on length of cycle, mid luteal phase)
- D3 FSH/LH
- Testosterone, prolactin, TFTs
- Rubella status
- Anti-mullerian hormone (test of ovarian reserve, not 1st line)
USS:
- PCO
- Can monitor follicular growth (generally not done)
LH hormone based urine predictor kits:
- OTC (indicate if LH surge has taken place)
TUBAL PATENCY:
- Laparoscopy and dye
- Hysterosalpingogram (less invasive, do this first)
What investigations would you do for subfertility in the male?
Semen analysis
List the WHO criteria for semen analysis
- Volume >1.5mls
- Sperm count >15 million/ml
- Progressive motility >32%
- Morphology >4% normal
How do we do semen analysis?
- Specimen needs to be produced by masturbation and not into a condom
- Done after 2-5 days of abstinence
- Specimen needs to be kept at body temperature, and bought to the lab within 1hr from production
What do we do if semen analysis is abnormal?
- Can repeat 3mths after initial analysis (allows time for cycle of spermatozoa formation to complete)
- If gross spermatozoal deficiency test should be repeat ASAP
List the causes of abnormal semen analysis?
- Unknown
- Smoking/alcohol/drugs
- Varicocele
- Antisperm antibodies
- Klinefelter’s syndrome
- CF mutation carrier
What are the general treatment options for subfertility?
- Weight loss
- Lifestyle advice
- Folic acid
How is tubal factor subfertility treated?
- Laparoscopic surgery if mild/endometriosis
2. IVF if fails or severe
What is the treatment for anovulation?
- Clomiphene
- Selective oestrogen receptor modulator (SERM). Causes release of GnRH by the hypothalamus
- SEs = Twins 10%, blurred vision, OHSS - Metformin
- Gonadotrophins
What is the surgical treatment of PCOS?
Ovarian diathermy
How can we treat male factor infertility?
- IUI
- IVF with or without ICSI
- DI
What to we use in cases of unexplained subfertility?
- IUI
2. IVF
What are the criteria for diagnosis of PCOS?
At least 2 of following 3 criteria must be met:
- Polycystic ovaries on ultrasound
- Irregular periods (>35days apart)
- Hirsutism - clinical (acne or excess body hair) and/or biochemical (raised serum testosterone)
List the clinical features of PCOS
- PCO
- Obese
- Acne
- Hirsutism
- Oligomenorrhea or amenorrhea
- Miscarriage more common
List the complications of PCOS
- T2DM
- GDM
- Endometrial cancer
How can we treat the other symptoms of PCOS besides infertility?
- Advice regarding diet and exercise
- COCP will normalise menstruation if fertility not required
- Anti-androgens (cyproterone acetate or spironolactone) effective for hirsutism but conception must be avoided
- Eflornithine - topical anti-androgen for facial hirsutism
What are the key points about Clomifene?
- Traditional 1st line ovulation drug in PCOS
- Limited to 6mths use (as anti-oestrogen)
- Only given at start of cycle - initiates follicular maturation
- Monitored by TVUS
- If no follicles develop dose increased in subsequent cycles
- If 3 or more follicles develop, cycle cancellation initiated to decrease risk of multiple pregnancy
What are the key points about metformin?
- Insulin sensitising drug used to restore ovulation
- Does not promote ovulation so no increase in multiple pregnancy
- Taken every day throughout cycle in multiple doses
- GI SEs common
- Treats hirsutism
What are the key points about laparoscopic ovarian diathermy?
- Second line tx
- As effective as gonadotrophins
- Lower multiple pregnancy rate
- Each ovary monopolar diathermised at a few points for a few seconds
- Tubal patency tested during same operation
What are the key points about gonadotrophin induction of ovulation?
- Used when first line treatments have failed
- Also given in hypothalamic hypogonadism when weight is normal
- Usually maturation of more than one follicle
- In PCOS low dose step-up regimen
- Follicular developments monitored via US
- Follicle of adequate size for ovulation - artificial stimulation of ovulation by injection of hCG or recombinant LH
List the side effects of ovulation induction
- Multiple pregnancy
- Ovarian hyperstimulation syndrome (OHSS)
- Ovarian and breast carcinoma
Define ovarian hyperstimulation syndrome (OHSS)
Overstimulation of the follicles in the ovaries and they get very large and painful. More common during IVF than standard ovulation induction
List the risk factors for OHSS
- Gonadotrophin stimulation
- Age <35yrs
- Previous OHSS
- Ovaries of polycystic morphology on US
How can we prevent OHSS?
- Use lowest effective dose of gonadotrophin doses
- US monitoring of follicular growth - if excessive withdrawal of gonadotrophins for a few days or cancellation of IVF cycle (withholding hCG injection)
What happens in severe cases of OHSS?
- Hypovolaemia
- Electrolyte disturbances
- Ascites
- Thromboembolism
- Pulmonary embolism
- CAN BE FATAL