INFERTILITY ASSOCIATED WITH PCOS Dr. Norlia Bahauddin Hospital 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 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

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