Table 1.

Summary of available Ovulation Induction (OI) techniques.

Intervention	Supplementary drug	OI Initiation (Day of Cycle)	Protocol	Protocol progression	Protocol monitoring	Expected result
Weight loss and lifestyle modifications	–	–	Loss around 5–10% of body weight (20–26)	–	–	•Reduce hyperinsulinemia, (27–31) • Increase insulin sensitivity, (27–31) • Restore ovulatory cycles, (27–31) • Improve reproductive outcomes including ovulation and menstrual cycle regulation (32).
Myo–Inositol	–	–	–	–	–	• Improving insulin sensitivity (33) • Increasing Sex Hormone Binding Globulin (SHBG) (33) • Decrease free Testosterone (33) • minimizing hyperandrogenic features (33). • Increase ovulation rates when compared with placebo or no treatment (33)
Clomiphene	–	Day 2–5	50 mg OD for 5 days–traditional	Progestin prescribed for lack of ovulation and cycle restart Increase by 50 mg for each cycle thereafter until response–Upper limit at 250 mg.	Serum progesterone levels, > 3 ng/mL between days 22 and 25 indicates successful ovulation	• Successful in 70–80% of women (34, 35) • Cumulative pregnancy rates of 70–75% are expected over 6–9 cycles of treatment (36, 37)
	–		50 mg OD for 5 days–“stair step”	Increase by 50 mg if lack of dominant follicle on ultrasound	Ultrasound sonography day 11–14, Repeat ultrasound 1 week after dose increase	• Significantly higher ovulation rates of 64% at 100 mg when compared to the traditional 22% at the same dose (38) • Shorter time to ovulation by 32–53 days when compared to the traditional method (38)
	Glucocorticoids	Day 5	Clomiphene 200 mg OD for 5 days Dexamethasone 2mg OD for 10 days	Clomiphene resistant women–no progression	Ultrasound sonography day 16 or 17	• 88% of women had successfully ovulated vs. 20% of in the control group (39) • Cumulative pregnancy rate 40.5% vs. 4.2% in the control group (39)
	Metformin	Day 3	Clomiphene 50 mg OD for 5 days Metformin 500 mg OD–gradually increase to 2g (1g BD)	Increase Clomiphene dose either after 5 weeks of anovulation or after a menses–Upper limit at 150 mg	If 2 consecutive serum progesterone levels > 5ng/mL then weekly pregnancy test until positive or menses occurred	• Clomiphene alone and Clomiphene with Metformin is superior to Metformin alone in live birth rate (40) • Comparable live birth rate in Clomiphene vs. Clomiphene with Metformin (40)
	Myo–Inositol	No available evidence/protocol in the literature for comparison with other protocols
Letrozole	–	Day 3–5	2.5 mg OD for 5 days	Increase by 2.5 mg for each cycle thereafter until response–Upper limit at 7.5 mg Max 5 cycles for each patient	Mid luteal progesterone >3 ng/mL	• Higher cumulative pregnancy rate (27.3% vs. 21.5%) and higher live birth (27.5% vs. 19.1%)(41) when compared to Clomiphene • Higher proportion of women achieve ovulation (88.5% vs. 76.6%), and a higher proportion of ovulations over total treatment (61.7% vs. 48.3%) when compared to Clomiphene (41)
Exogenous Gonadotropins	–	Day 3–5	75IU hMG/rFSH OD for 5 days–conventional protocol	Increase by 75IU hMG/rFSH until response Triggered with 5,000–10,000 IU hCG	Elevated levels of Estradiol when compared to background Ultrasound sonography for Follicular visualization and triggering	• Cumulative conception rates of around 90% and cumulative live birth rates of 85% after 12 cycles (42) • Risk for OHSS and multifetal pregnancy (43, 44)
	–		37.5–75IU hMG/rFSH OD for 8–14 days–chronic low dose	Increase by 37.5–75IU hMG/rFSH until response Triggered with 5,000–10,000 IU hCG		• Similar cumulative pregnancy and live birth rate with conventional protocol (45–49) • Smaller OHSS and multifetal pregnancy risk than conventional protocol (45–49)
Laparoscopic Ovarian Drilling	–	–	–	Often reserved for medication resistant women–No progression	–	• Similar in live birth rates compared to clomiphene citrate and metformin, gonadotrophins (50). • Lower live birth rates when compared to letrozole (50).