More Pregnancies With Weight Loss Before IVF

Women with obesity who lost weight prior to in vitro fertilization (IVF) had increased pregnancy rates, especially unassisted conceptions, a systematic review and meta-analysis has found.

The studies reviewed were small and heterogeneous, making it difficult to determine which weight loss interventions had the most efficacy, according to the authors. Still, they concluded that weight loss in this cohort might “negate the need for treatment, and does not seem to increase the risk for pregnancy loss, although evidence on the effect on live births was unclear.”

The results were published online August 12 in the Annals of Internal Medicine. 

Obesity is associated with ovulatory dysfunction, reduced ovarian responsiveness to agents that induce ovulation, altered oocyte and endometrial function, and lower birth rates after IVF, according to an opinion published by the Practice Committee of the American Society for Reproductive Medicine in 2021.

Previously, it was unknown whether weight loss before IVF improves reproductive outcomes, so Moscho Michalopoulou, MSc, DPhil, a behavioral scientist at Oxford University in the United Kingdom, and a team of researchers reviewed 12 randomized controlled studies (RCTs) of 1921 women with obesity who were offered a weight loss intervention before planned IVF. 

The studies included in the analysis were of women in upper-middle or high-income countries who had a median body mass index of 33.6 kg/m². They were typically in their early 30s, and their weight loss prior to conception tended to be modest across the studies included. Nearly a quarter of women from nine studies had polycystic ovary syndrome. Weight loss in this PCOS population was associated with fewer unassisted conceptions. 

There were numerous weight loss interventions across the RCTs, and their median duration of an active weight loss phase was 12 weeks (range 5 – 24 weeks). 

Controls across the studies in the analysis received usual care, yet in six studies they received no or minimal intervention. In the remaining six studies, usual care was a less intense weight loss intervention than in the study arm. Participants across all intervention groups lost 4 kg more than controls, the researchers found.

The difference in weight change between groups was larger when interventions were compared with no or minimal intervention rather than to an active control. The average follow-up for reproductive outcomes was 9.3 months (range 1.3 – 18 months) for intervention groups vs 11.2 months (range 4.3 – 24 months) for controls.

Ten studies reported unassisted pregnancy rates (1466 participants). Eight studies favored intervention; however, most studies had few unassisted pregnancies, resulting in wide confidence intervals. 

Overall, the investigators found that weight loss interventions before IVF were associated with greater unassisted pregnancy rates (relative risk, 1.47; 95% CI, 1.26 – 1.73). The effect size was greater in the RCTs with controls involving no or minimal intervention vs an active weight loss comparator, although the small number of studies and events limited formal comparison. 

No consistent pattern was observed when studies were sorted by the difference in weight change between groups, age, or baseline BMI, but the study authors found a tendency for fewer unassisted pregnancies with an increasing proportion of women with PCOS in the sample.

“There was inconclusive evidence on the effect of weight loss interventions on treatment-induced pregnancies. Overall, evidence on the association between weight loss interventions before IVF and live births was uncertain, although there was moderate certainty of no association with pregnancy loss,” the investigators write. 

The authors noted that a weakness in their study was a lack of follow-up on pregnancy outcomes. “Unfortunately, fewer studies reported live birth outcomes, not all studies followed up on unassisted conceptions to determine live birth, and evidence on live births was further limited by heterogeneity in study design and clinical characteristics of recruited populations,” the authors write.

Another deficit in the study, according to the authors, was that the studies reviewed had “marked variability in eligibility and in participant characteristics that affect IVF success and could have influenced the effect of weight loss interventions on outcomes.”

According to an accompanying editorial written by Alan S. Penzias, MD,“[The authors] highlight for future investigators the need for studies that include outcomes, including pregnancy loss and live birth, for both medically assisted and unassisted pregnancies.” 

Penzias directs the Fellowship Program in Reproductive Endocrinology and Infertility at the Boston IVF/Beth Israel Deaconess Medical Center, and is an associate professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School, Boston, Massachusetts. 

The women in the studies Michalopoulou and her colleagues analyzed tended to be in their early 30s, which Penzias focused on in his editorial. “A woman’s age is the strongest predictor of successfully becoming pregnant,” he writes. “The association of increasing age with reduced fecundity is so strong that some advocate consideration of IVF as a first-line treatment strategy in women older than 38 to 40 years. It is critical to balance the time it takes to achieve weight loss and the benefit of weight loss on medically unassisted conception.” 

Penzias suggested that in addition to a woman’s age, her preferred family size, which cannot be determined by weight loss, must also be factored in when deciding whether to use IVF.

“It is important to understand that once an oocyte is retrieved via IVF, any embryo created from its fertilization will always carry the success rate associated with the woman’s age at the time of retrieval,” Penzias writes. 

For Cate Varney, DO, an associate professor in the Department of Family Medicine at University of Virginia School of Medicine in Charlottesville, the age of the woman seeking to become pregnant does matter, but that “it is well-established that obesity plays a significant role in infertility. There is a gap in the data between the association and modifiable risk,” she told Medscape Medical News. 

“The timing and amount of clinically meaningful weight loss will be important to identify so we can clarify the trade-offs between delaying IVF for weight loss vs age-related fertility decline,” said Varney, who is also the obesity medicine director at UVA Health.

The study was supported by the National Institute for Health and Care Research Applied Research Collaboration Oxford and Thames Valley. The study authors and editorialist Penzias reported no relevant financial relationships. Varney is an advisor and in the speaker’s bureau for Eli Lilly.