This blog is the second part of Dr. Laurence Jacobs’ series on Polycystic Ovary Syndrome (PCOS). In part one, he discussed the signs, symptoms and diagnostic criteria for PCOS.
In this follow-up, Dr. Jacobs outlines the latest PCOS treatment guidelines, from lifestyle modifications and metabolic therapies to fertility medications and assisted reproductive technology (ART). PCOS is a complicated disease, understand your treatment options based on your fertility goals.
About PCOS
As discussed in part I, Polycystic ovary syndrome (PCOS) is characterized by a combination of excess hair growth, ovulatory dysfunction, and polycystic ovarian morphology on vaginal ultrasound, associated with insulin resistance. Latest treatment guidelines focus on lifestyle modifications, medications, and careful fertility care, including the role of newer agents such as GLP-1 receptor agonists.
Lifestyle Modification for Preconception Health
Lifestyle intervention, overlooked by many physicians for decades, remains the cornerstone of PCOS management. Weight management, improved nutrition, and physical activity are consistently associated with improved metabolic health, ovulation, and higher pregnancy rates. Even modest weight loss of 5–10% can often restore ovulation and/or improve pregnancy rates naturally, as well as with medication/IUI and IVF treatments. Programs that offer qualified medical nutrition therapy (MNT), regular exercise training, and behavioral modification via personalized provider telehealth have excellent outcomes for preconception health (WINFertility and OvumHealth).
Medical/Surgical Therapies for Weight and Metabolic Management
Metformin continues to be used as first-line pharmacologic therapy for metabolic abnormalities, such as impaired glucose tolerance and insulin resistance in women with PCOS. The supplement Myo-Inositol has also demonstrated significant benefit in dealing with insulin resistance.
GLP-1 receptor agonists (tirzepatide, semaglutide and related agents) are a major addition in the treatment options for weight loss. These medications significantly reduce body weight, and insulin resistance in PCOS patients. Current evidence also suggests improvements in menstrual cycle regularity and ovulation. They can be helpful as an adjunct to lifestyle changes for overweight/obese women but are most effective when used in conjunction with lifestyle improvements. Careful collaborative decision making is vital, as side effects (nausea, vomiting, pancreatitis, gallbladder disease, etc.), high costs with little insurance coverage and long-term safety remain an issue. Since pregnancy safety studies are lacking, contraception should always be utilized when GLP-1s are used in women planning pregnancy in the future and stopped when attempting conception.
Bariatric surgery may be considered for women with PCOS and severe obesity who meet criteria for surgical weight management. While not specific to PCOS, weight reduction from bariatric surgery may restore ovulation and improve metabolic health.
Laparoscopic ovarian drilling, another surgical option, has a very limited role in modern infertility practices, but in the past has helped some women by reducing ovarian testosterone and other male hormones (androgens). This option is rarely used today due to costs and potential damage to ovaries leading to adhesions.
Ovulation Induction and Infertility Management
Infertility is very common in PCOS, primarily due to anovulation and/or poor egg quality.
Letrozole has become the first-line medication therapy for ovulation induction in women with PCOS and anovulation, among most Reproductive Endocrine/Infertility specialists and many Ob/Gyns. Many well-controlled randomized studies have demonstrated higher ovulation, pregnancy, and live birth rates, as well as lower multiple birth rates with letrozole compared with clomiphene citrate.
Clomiphene citrate (Clomid) remains a popular option, particularly among Ob/Gyns. Combination therapy with clomiphene plus Metformin improves ovulation and live birth rates compared to clomiphene alone.
Metformin when used alone is less effective for ovulation induction but may be considered in combination with Letrozole and/or Gonadotropin medications (Menopur, Gonal F and Follistim), when doing ovarian stimulation for ovulation induction or IVF.
Gonadotropins are second-line therapy when oral ovulation induction fails. Careful monitoring is required to minimize the risk of ovarian hyperstimulation (OHSS) and multiple pregnancies. IVF is far more effective and safer regarding multiples.
Assisted Reproductive Technology (ART) and IVF
In vitro fertilization (IVF) is often reserved for women who fail less invasive ovulation induction therapies or who have additional infertility factors such as tubal disease or male factor infertility. In PCOS, IVF requires particular caution due to the high risk of OHSS. The newest guidelines emphasize the use of GnRH antagonist protocols (Ganirelix; Cetrotide) and individualized low dose stimulation strategies with Lupron triggers to minimize this OHSS risk. Pre-treatment with metformin may also reduce OHSS risk in women still undergoing IVF with GnRH agonist protocols. As noted above, Preconception care—including optimization of weight, hormones and metabolic status—is recommended prior to doing ART.
A Comprehensive Approach to PCOS Treatment
PCOS is a complex condition requiring an individualized, comprehensive approach. Preconception health with lifestyle modification remains first-line therapy. Medication therapy has improved. Metformin and Myo-Inositol supplements maintain their roles. GLP-1 receptor agonists, with proper counseling and informed consent, represent a new option for weight loss and metabolic improvement.
For infertility treatments, letrozole is clearly the first-line option for ovulation induction. Clomiphene, metformin (alone), and gonadotropins are occasionally used. IVF is very effective but requires careful strategies to minimize OHSS risk. Single frozen embryo transfers greatly reduce the risk of multiples. (1-2% identical, if embryo splits).
Expert Care for PCOS
Dr. Jacobs has helped women manage their PCOS for more than 40 years and was formerly the Director of the PCOS Center of Excellence. He understands firsthand how medications, supplements and lifestyle modifications can profoundly impact the health and fertility of PCOS patients.
If you think you may have PCOS or are struggling with symptoms, Dr. Jacobs and our team can help with the correct diagnosis and treatment options. Click here to schedule a consultation.
To understand more about PCOS, read part one of this blog discussing symptoms and diagnosis.
