Ketogenic diet boosts IVF success for women with PCOS, study reveals

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Oct 24 2023

A recent study in the journal Nutrients examines the impact of dietary interventions on the success of in vitro fertilization (IVF) in women with a high body mass and polycystic ovarian syndrome (PCOS).

Study: The impact of nutritional therapy in the management of overweight/obese PCOS patient candidates for IVF. Image Credit: Freebird7977 / Shutterstock.com

Introduction

Polycystic ovarian syndrome (PCOS) is a metabolic-reproductive disease that is the most common hormonal disorder affecting females. In about 75% of women with PCOS, ovulation is either partially or entirely disrupted, thus increasing the risk of anovulatory infertility in affected women.

PCOS is also associated with a higher risk of metabolic dysfunction, including insulin resistance, type 2 diabetes, metabolic syndrome, and cardiovascular disease (CVD). This increased risk can be attributed to greater fat deposition beneath the skin and in the abdomen, likely due to increased androgen levels.

Excessive body mass is known to reduce the efficacy of assisted reproduction technologies (ART) like IVF. A high body mass index (BMI) is associated with a seven-fold greater risk of adverse effects such as ovarian hyperstimulation syndrome (OHSS) during IVF. Ovulation induction is also more difficult with a higher BMI.  

These effects may be attributed to the relative resistance of the ovary to stimulation by follicle-stimulating hormone (FSH), which requires higher levels of FSH to be achieved for successful follicle development. This process also yields fewer oocytes and lower serum estradiol levels compared to non-PCOS women.

Other subtle hormonal alterations may underlie the observed deterioration in oocyte and embryo quality and rate of implantation. This affects the rate of successful IVF and obstetric outcomes. For example, the rates of miscarriage, congenital anomalies, preterm delivery, and intrauterine death are all increased among obese or overweight mothers.

Mothers with a high BMI are also more likely to have children with a higher long-term risk of several chronic conditions such as diabetes, stroke and other CVDs, cognitive dysfunction, and asthma.

Approaches to PCOS-related infertility include drugs, surgery, lifestyle changes, and IVF. IVF is used when ovulation induction has not succeeded or if male subfertility or tubal infertility complicates the issue.

Weight loss of 5% or more is effective in treating PCOS, as it enhances reproductive function even without ART, reduces chronic inflammation, and improves metabolic parameters. Fat depots in the body are also an important source of hormones that secrete androgens. Low-carbohydrate dietary regimens may also reduce or reverse insulin resistance and inflammation.

In the current study, researchers explore the benefits of interventions that reduce body mass in women with PCOS-related infertility who are IVF candidates. These interventions included the Mediterranean diet (MD) and a very low-calorie ketogenic diet (VLCKD).

What did the study show?

The study included a small sample of 84 PCOS patients who were either overweight or obese. Study participants were put on either the VLCKD or MD and subsequently examined for changes in weight, hormonal profile, and metabolic thresholds.

Patients on the VLCKD lost significant weight, as reflected in the BMI compared to MD patients at three and four months. The body circumference (hip and waist), which is a predictor of visceral and subcutaneous fat, was also reduced significantly in VLCKD patients.

Patients consuming the VLCKD exhibited reduced hip circumference measurements by nine and 11 cm at three and four months, respectively. Abdominal circumference measurements decreased by eight and 11 cm, respectively, which was double that in the MD group. Waist circumference measurements declined by nine and 12 cm in the VLCKD group compared to half of these values in the MD group values.

The HOMA index for metabolic health also declined among VLCKD patients at both time points by four-fold compared to the MD group. Healthy cholesterol levels increased in both groups by 120 days but to a greater extent in the VLCKD group. A similar change was observed for the antral follicle count (AFC), a risk factor for OHSS, along with PCOS.

Anti-Mullerian hormone (AMH) levels declined in the VLCKD cohort, thus reflecting a change in PCOS profile. Androgen levels also declined with both VLCKD and MD; however, the magnitude of the reduction was greater with the VLCKD diet. FSH and luteinizing hormone (LH) serum levels did not differ significantly; however, the FSH/LH ratio improved by 120 days in both groups.

Menstrual cycles became more regular in about 50% of women at 90 days in the VLCKD group and 70% after 120 days. No patient reported a worsening in their menstruation regularity. The corresponding figures for the MD group were 17% and 26%, respectively, while worsening was reported in 2% of cases.

About 75% and 90% of women on the VLCKD diet moved from amenorrhea to regular or irregular cycles at 90 and 120 days, respectively, compared to about 50% and 60% with the MD.

The number of new OHSS cases was lower among VLCKD patients at 27% compared to 68% among those on MD. Therefore, both dietary approaches appear to indirectly improve body composition as reflected by various body mass measurements, as well as reproductive outcomes in terms of better ovarian function, more regular periods, and a lower rate of OHSS during IVF cycles.

Our results show that greater weight loss, and thus greater visceral fat loss, is accompanied by a significant improvement in the metabolic profile in VLCKD PCOS patients.”

The positive impact of the VLCKD on metabolism may be due to higher muscle metabolism and greater fat loss. This may be attributed to the increased levels of adrenergic hormones that promote a higher basal metabolic rate, slow down the breakdown of muscle protein, and promote increased muscle growth. Future studies are needed to validate these findings by directly measuring changes in muscle mass as compared to fat mass in individuals on either of these diets.

What are the implications?

The study participants expressed satisfaction with the outcomes in terms of body composition change and their ability to adhere to the diet. This may promote the adoption of these health-promoting lifestyles, thereby restoring fertility and enhancing success rates following IVF in PCOS patients with high body mass.

VLCKD is a dietary regimen that achieves a BMI compatible with access to IVF therapy in the short term [that] results in greater patient compliance and is more suitable for the needs of an IVF center.”

VLCKD appears to improve reproductive health and promote safer IVF. The low carbohydrate intake of these diets may also mitigate or reverse metabolic dysfunction and thus improve the individual's long-term health.