What are the best treatment options for a woman with Polycystic Ovary Syndrome (PCOS) who wants to get pregnant?

Treatment for Women with PCOS Seeking Pregnancy

Start with lifestyle modification targeting 5% weight loss, then proceed directly to clomiphene citrate as first-line ovulation induction, as this achieves an 80% ovulation rate and 50% conception rate in women with PCOS. 1, 2, 3

Initial Management: Lifestyle Modification

Weight loss is the cornerstone of treatment and must be addressed first. Even modest weight reduction of 5% of initial body weight improves both metabolic and reproductive abnormalities in PCOS, including ovulation and pregnancy rates. 1, 2

• Implement a structured program with 30% energy deficit or 500-750 kcal/day reduction 2
• Combine dietary modification with regular exercise (150 minutes per week or 30 minutes daily of moderate intensity) 1, 2
• Weight loss improves response to ovulation-inducing medications and fertility treatments 4, 5

Common pitfall: Do not delay pharmacologic ovulation induction indefinitely while pursuing weight loss—proceed to medication after establishing a weight management plan, especially if the patient has been attempting lifestyle changes for 6 months without success. 1, 4

First-Line Pharmacologic Treatment: Clomiphene Citrate

Clomiphene citrate is the established first-line medication for ovulation induction in PCOS. 1, 2, 3

• Approximately 80% of women with PCOS ovulate on clomiphene, and half of those who ovulate will conceive 1, 2
• Start clomiphene on day 5 of the menstrual cycle 3
• Limit treatment to approximately 6 total cycles (including 3 ovulatory cycles) 3
• Properly timed intercourse in relationship to ovulation is critical—use basal body temperature charting or ovulation predictor kits 3

Critical caveat: Before starting clomiphene, confirm the patient is not pregnant, has no ovarian cysts (except polycystic ovaries), has no abnormal vaginal bleeding, and has normal liver function. 3

Second-Line Treatment: Low-Dose Gonadotropins

If clomiphene fails after appropriate trials, use low-dose gonadotropin therapy rather than high-dose protocols. 1, 2

• Low-dose gonadotropins induce high rates of monofollicular development with lower risk of ovarian hyperstimulation syndrome 1, 2
• This is preferred over high-dose regimens which carry excessive hyperstimulation risk 1

Role of Insulin-Sensitizing Agents

Metformin improves insulin sensitivity and can be used adjunctively, though its primary role is metabolic rather than fertility enhancement. 1, 2, 4

• Metformin appears safe during pregnancy, though documentation on early pregnancy effects is limited 1, 6
• It improves glucose tolerance and reduces diabetes/cardiovascular risk factors in PCOS 1, 2
• Metformin improves ovulation frequency, but effects on conception rates are less established than clomiphene 1
• Consider metformin particularly in women with impaired glucose tolerance or metabolic syndrome features 4

Important consideration: Stop weight loss medications before attempting conception. 1

Pre-Conception Optimization

Screen and treat metabolic abnormalities before attempting pregnancy. 2, 4

• Obtain fasting glucose and lipid profile to assess metabolic risk 2
• Screen for type 2 diabetes, as women with PCOS have 7.5-10% prevalence and rapid progression rates 4
• Evaluate and treat hypertension, as PCOS increases pre-eclampsia risk 4
• Start folic acid 5 mg daily (higher dose than standard prenatal) and continue through first trimester 1

Critical evaluation: Assess for other infertility factors including semen analysis, tubal patency, and thyroid/prolactin disorders before attributing infertility solely to PCOS. 2, 3

Surgical Options

Bariatric surgery can be considered for women with BMI ≥35 kg/m² who remain anovulatory and infertile despite 6 months of intensive lifestyle intervention. 1

• However, conflicting guidelines exist—one recommends against bariatric surgery specifically for infertility treatment 1
• If bariatric surgery was performed pre-pregnancy, ensure ongoing dietitian follow-up 1

Laparoscopic ovarian drilling has undetermined benefit and role according to ACOG, though it may be considered as an alternative to gonadotropins if laparoscopy is needed for another indication. 1, 5

Pregnancy Risk Counseling

Counsel patients about increased pregnancy risks associated with PCOS. 1, 2

• Higher rates of gestational diabetes (screen early in pregnancy) 1, 4
• Increased risk of pre-eclampsia and placental abruption 4
• Plan for early booking visit and appropriate prenatal surveillance 1