INFERTILITY ASSOCIATED WITH PCOS

Dr. Norlia BahauddinHospital Kajang

Mdm SH

• A 28 year old Malay, nulliparous, married for 2 years.

• No medical illness.• Initially regular menses• Past 2 years, menses became

oligomenorrhoeic, every 12-20 weeks apart, lasting 2-3 days

• Increase in weight within 2 years• She is a non smoker and non drinker• The couple had regular unprotected

intercourse • Husband healthy, no erectile dysfunction or

premature ejaculation

• Obese lady, BMI: 34kg/m². Acne present. No hirsutism seen or signs of insulin resistant such as acanthosis nigrican seen.

• Ultrasound examination noted polycystic ovaries• Investigation result– FSH/LH: 5.7/9.1– Mid Luteal progesterone: 0.22ng/ml– T4/TSH: 2.67/17.2– Testosterone: 2.85nmol/L– MGTT: Fasting4.6mmol/L / 2H postprandial 8.5mmol/L– Pap smear: NILM– SFA: normal

• Advised to reduce weight, referred to a dietician.

• Commenced on ovulation induction.• Metformin given in view of impaired glucose

tolerance test. • She was started on clomiphene citrate for

3cycles (50mg od x1, 100mg od x2), however failed (no dominant follicle seen during follicular tracking).

• Proceeded for laparoscopic dye test and ovarian drilling. Intraoperatively noted right polyscystic ovary. Both fallopian tubes patent.

• Given another cycle of clomid 100mg od, which failed .

• Then given 1 cycle of S/C Puregon(75iu x5/7,150iu x 7/7)

• Follicular tracking showed a dominant follicle right ovary (18mm).Triggered with HCG (IM Pregnyl 10000iu) followed by IUI 36 hours later.

• Unfortunately, subsequent follow up noted an ectopic pregnancy and a diagnostic laparoscope showed a left tubal pregnancy and left salphyngectomy was done.

DISCUSSION

• Definition of PCOS, with two out of three criteria being diagnostic:– polycystic ovaries (12 or more peripheral

follicles, 2-9mm ) or increased ovarian volume (greater than 10 cm3)

– oligo- or anovulation– clinical and/or biochemical signs of

hyperandrogenism

• PCOS is associated with hyperinsulinemia, obesity, hypertension, dyslipidemia, and an increased prothrombotic state.

• There is also an increased risk of type 2 diabetes and impaired glucose tolerance, infertility and sleep apnea.

• Anovulation is common among women with PCOS.

• Hyperandrogenism, in conjuction with hyperinsulinaemia are cardinal features of PCOS .

• Follicular testosterone level have been shown to be elevated in PCOS.

• High androgen levels may contribute to lower fertilization rates.

• Glycodelin is a secretory protein from the endometrium and is a marker of endometrial receptivity.

• High androgen levels in PCOS attribute to a reduction in glycodelin and therefore a reduction in endometrial receptivity.

• Management of infertility in PCOS includes lifestyle modification and assisted reproductive technology such as ovulation induction.

• For overweight women with PCOS who are anovulatory, diet adjustments and weight loss are associated with resumption of spontaneous ovulation in some women

• Central obesity is a major factor influencing outcomes of both treatment of symptoms and infertility in women with PCOS.

• Obesity is associated with increase in miscarriage, gonadotrophin resistance and reduction in oocyte number.

• Clomiphene citrate is the first-line treatment in anovulatory patients with PCOS.

• The cumulative pregnancy rate with clomiphene citrate after 6 months of treatment is between 40% and 50%.

• Women who remain anovulatory can be stimulated with low dose gonadotropins.

• Patient with PCOS undegoing IVF treatment are at a higher risk to develop OHSS.

• Higher estradiol concentration and oocyte numbers are found in those who develop OHSS.

• Metformin as a first line agent in ovulation induction is less effective than clomiphene; lower ovulation and pregnancy rates

• However, metformin benefits women with clomiphene resistance

• Non obese PCOS women benefit the most from metformin; improves live birth rate

• Metformin use is also associated with reduced OHSS

• Metformin reduces serum testosterone and free androgen index, this improves folliculogenesis

• Serum VEGF and estradiol levels are lower in those on metformin, this helps reduce risk of OHSS

• Surgery can be attempted in cases where ovaries are resistant to stimulation/ovulation induction.

• The polycystic ovaries can be treated with a laparoscopic procedure called "ovarian drilling" (A total of 3 to 10 punctures, 7 to 8 mm in depth are made in each ovary depending on its size. Each penetration lasts 4 to 5 seconds).

• This results in resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or FSH.

• Unlike ovarian stimulation treatment, drilling is not associated with an increased risk of multiple pregnancy.

• LOD destroys ovarian androgen producing tissue and reduces peripheral conversion of androgens to estrogens.

• A fall in the serum levels of androgens and LH and an increase in FSH levels occur.

• This converts an adverse androgen dominant intrafollicular environment to an estrogenic one and restores the hormonal environment.

• This can restore ovulatory function

• Anti mullerian hormone (AMH) is a biomarker that has been investigated as a risk factor for OHSS

• Secreted by granulosa cells in pre-antral and small antral follicles

• Used to estimate ovarian reserve and predict ovarian response to gonadotrophin stimulation

• Higher AMH levels is associated with OHSS

THANK YOU