Weight Regain following Bariatric Surgery and in vitro Fertilization Outcomes.

From 2013 to 2022, 94 women with a history of BS underwent IVF at our division. Of these, 78 were included in the analysis. Sixteen were excluded: 11 underwent the procedure for fertility preservation purposes, and five women underwent PGT-M and had no embryos suitable for transfer. Seventy-eight women underwent 268 oocyte pickup cycles (median, 2; IQR 1–5) during a median follow-up of 18.8 months (IQR 9.4–28.5 months). The median age of the women in the cohort who underwent their first IVF cycle was 37 years (IQR 31–40), and 28.2% reported active tobacco smoking. Thirty-six women (46.2%) had previously conceived, and 26 (33.3%) had delivered at least one child. Patients’ demographics are shown in Table 1 . Patients’ demographics Continuous and ordinal variables are presented as mean (SD)/median (IQR) and categorical variables as number and percentage. Seventy participants underwent one BS, and eight had a history of two BS. Of them, 3 gained less than 3 kg/m 2 and 5 gained more than 3 kg/m 2 . There was no significant difference in BMI regain between women who underwent one or two BS ( p = 0.127). The underlying reasons for IVF treatment were unexplained infertility (25.6%), male partner infertility (24.4%), anovulation (16.7%), diminished ovarian reserve (15.4%), PGT-M (10.3%), mechanical factors (5.1%), and endometriosis (2.6%). Following BS, women lost significant weight with a median BMI reduction of 15.9 kg/m 2 (median 43.5 kg/m 2 , IQR 40.6–48.2 vs. 27.6 kg/m 2 , IQR 23.7–32.1; p < 0.001). The median BMI at the first IVF treatment following surgery was 30.6 kg/m 2 (IQR 25.2–35.1). The median time from surgery to the first IVF treatment was 3 years (IQR 2–7 years). Twenty-eight patients (35.9%) regained at least three points of BMI (approximately 5 kg) from the nadir BMI after surgery to the beginning of IVF treatments. Patient age, baseline BMI, and nadir BMI after BS did not differ between the two groups ( Table 1 ). The groups did not differ in the number of oocytes retrieved, mature oocytes, fertilized oocytes, or top-quality embryos on day 3 after the first treatment after BS. During the 36-month study period, 89.4% of the women had positive β-hCG after embryo transfer, 69.9% within the first year, and the remainder during the second year of follow-up ( Table 2 ). No positive β-hCG results were reported during the third year of follow-up. The median time for positive β-hCG was 2.97 months (95% CI: 1.04–4.89 months, Fig. 1 a). The median time for positive β-hCG was not significantly different between women who regained less than three points of BMI and those who regained more (median 2.60 months, 95% CI: 0.26–4.94 vs. 3.73, 95% CI: 1.32–6.15, p = 0.324, Fig. 2 a, Table 2 ). Cumulative pregnancy rates according to BMI regain Cumulative pregnancy rates of positive β-hCG ( a ), clinical pregnancy ( b ), and live birth ( c ). Cumulative pregnancy rates of positive β-hCG ( a ), clinical pregnancy ( b ), and live birth ( c ) in women who gained less than 3 kg/m 2 and in women who gained more. During the study period, 78.9% of the women had a clinical pregnancy after embryo transfer, 63.7% within the first year, and the remainder during the second year of follow-up ( Table 2 ). No clinical pregnancies were reported during the third year of the follow-up. The median time for a clinical pregnancy was 7.1 months (95% CI: 3.56–10.91 months, Fig. 1 b). When stratified by the extent of weight gain after BS, in women who regained less than three points of BMI, the median time for a clinical pregnancy tended to be shorter (median 5.83 months) than in women who regained more weight (median 9.33 months, p = 0.052). The 36-monthly cumulative clinical pregnancy rate was 89.6% in women who regained less than three points of BMI compared to 60.9% in those who regained more ( Fig. 2 b, Table 2 ). After adjusting for age and current BMI status (≥30 kg/m 2 ), women who regained <three points of BMI were approximately two times more likely to have a clinical pregnancy during a follow-up of 36 months (HR 1.967, 95%: CI: 1.026–3.771, p = 0.042). Maternal age and obesity were not significantly associated with clinical pregnancy ( p = 0.105 and p = 0.672, respectively). A total of 16 women from the cohort underwent missed abortion. All of them lost the pregnancy during the first trimester. Of them, 56.3% ( n = 9) did not gain more than 3 kg/m 2 and 43.7% ( n = 7) gained more than 3 kg/m 2 ( p = 0.804). During the study period, 50.8% of the patients had a live birth after embryo transfer, 45.5% within the first year, and the remainder within 2 years of treatment ( Table 2 ). The median time to live birth was 20.2 months ( Fig. 1 c). The median time for live birth from the first IVF treatment following BS was 8.87 months in women who regained less than three points of BMI, while in women who regained three or more points, the median time was not reached during the 36 months of follow-up. The 36-month cumulative live birth rate (CLBR) was 64.5% in women who regained less than three points of BMI compared with 27.4% in the other group ( p = 0.019, Fig. 2 c, Table 2 ). After adjusting for women’s age and current BMI status (≥30 kg/m 2 ), those who regained <three points of BMI were approximately three times more likely to have a live birth during a 36-month follow-up period (HR 2.864, 95% CI: 1.196–6.859, p = 0.018). Older maternal age was inversely correlated with the live birth rate (HR 0.914, 95% CI: 0.865–0.965, p = 0.001). Obesity was not associated with the live birth rate ( p = 0.841). Women who regained ≥three points of BMI had a longer interval from the BS to the first IVF treatment than women who regained <three points of BMI (5.3 years vs. 3.9 years, p = 0.045); however, after evaluation, there was no association between time from BS to the first IVF and treatment outcomes (positive β-hCG [ p = 0.154], clinical pregnancy [ p = 0.914], or live birth rate [ p = 0.440]). The percentage of obese women (BMI ≥30) was significantly higher among those who regained ≥three points of BMI (75% vs. 42%) ( p = 0.05) compared with women who regained <three points in BMI ( Table 1 ). No association was found between obesity in the initiation of IVF treatments and the studied outcomes (positive β-hCG [ p = 0.759], clinical pregnancy [ p = 0.823], and live birth rate [ p = 0.303]).

Our study underscores the negative consequences of weight regain on IVF outcome. This suggests that weight maintenance and relatively early IVF treatment after BS should be recommended to improve pregnancy outcomes.

Our cohort study showed that 89.4%, 78.9%, and 50.8% of the women had a positive β-hCG test, clinical pregnancy, and live birth following BS, respectively. All pregnancies occurred within the first 2 years after starting IVF treatment. The cumulative chances over time for positive β-hCG were 69.9% after 1 year of IVF and 89.4% after 2 years. The cumulative chance for clinical pregnancy was 63.7% and 78.9%, and the cumulative chance for live births was 45.5% and 50.8%, for one and 2 years of trials, respectively. No additional pregnancies occurred if the patient continued IVF treatment for more than 2 years, up to a 3-year follow-up ( Table 2 ). Almost 65% of women succeeded in maintaining their nadir BMI following BS before starting IVF treatment. Women who could maintain their nadir BMI following BS had almost double the chance to achieve a clinical pregnancy and approximately triple the chance for live birth compared to those who regained at least three points of BMI ( Table 2 ). There is conflicting evidence regarding the effects of BS on IVF treatment outcomes. In a recent Swedish national register-based case-control study, the CLBR after the first IVF treatment cycle was compared between 153 women who underwent BS and 744 non-operated controls. Patients were matched for age, parity, and BMI at treatment. There was no significant difference in CLBR between the two groups (29.4% vs. 33.1%) [ 14 ]. In contrast, multicenter research conducted in France compared the CLBR of the first IVF treatment among women after BS to two age-matched groups of non-operated women matched to cases by postoperative BMI and non-operated severely obese women (mean BMI = 37.7 kg/m 2 ). There was no significant difference in positive β-hCG levels between the groups. However, the live birth rate per transfer in obese patients was significantly lower than in the other two groups ( p = 0.0167). The same study showed that a one-unit decrease in BMI increased the chances of live birth by 9%, independent of BS [ 13 ], suggesting that access weight is deleterious to IVF treatment, and correcting it by BS can improve treatment outcomes. Although significant amounts of excess body weight can be lost in a short time, they have potential drawbacks. Operative complications are not unusual, and several cases have indicated an increased risk of intestinal hernias, volvulus, or obstruction among pregnant women with previous BS [ 18 ]. The procedure may cause nutritional deficiencies in iron, vitamin B12, folate, calcium, and fat-soluble vitamins A, D, E, K. Inadequate maternal nutrition is a common early complication of the surgery and can disrupt the well-being of a growing fetus. For this reason, many practitioners advise patients to delay pregnancy for 1–2 years after surgery [ 10 , 11 ]. The median time from surgery to the first IVF treatment in our cohort was 3 years (IQR 1.9–7 years). BS, a potent means of weight reduction, improves the rate of weight regain; however, a significant weight increase still occurs within 2–5 years in 25–35% of patients following BS [ 16 , 17 ]. This is the first study to examine the effect of weight regain after BS on IVF outcomes. The high prevalence of weight regain after BS, along with our essential finding that a relatively small regain is sufficient to negatively affect the rates of both clinical pregnancies and live births, is disturbing and merits medical attention. Our study suggests rates and a detailed timeframe for pregnancy and live births among patients undergoing IVF after BS for both physicians and patients. Moreover, we present the effect of weight regain on the results of IVF treatment in this population. This effect should be discussed with the patients at the beginning of the process and monitored by physicians during treatment. The primary effect of weight regain presented in this study requires, in addition to awareness and monitoring, a solution for patients to allow the maintenance of weight loss. Several studies have demonstrated the ability of anti-obesity medications to treat weight regain and help maintain weight loss after BS [ 16 ]. Recently, GLP-1 analogs have emerged as potent treatments for weight loss and maintenance [ 19 – 21 ]. Furthermore, several recent studies have shown that GLP-1 analogs effectively reduce and maintain weight after BS [ 22 , 23 ]. Therefore, anti-obesity medications should be considered for facilitating weight maintenance and treatment of weight regain in patients after BS seeking fertility treatment. Our study had some limitations. First, although the sample size was small, the same medical center treated all patients and had a similar IVF laboratory. Second, the multivariable analysis did not include the number of oocytes retrieved, mature oocytes, fertilized oocytes, or day 3 top-quality embryos. As the number of embryos transferred and oocyte retrievals are multifactorial and affected by the department policy, we decided to evaluate only the time to pregnancy and not the number of IVF cycles. However, we compared these IVF parameters (from IVF cycles) between the two groups, and no difference was observed. In addition, weight was measured at the beginning of the first IVF cycle, and we do not have the BMI at the second IVF cycle. As women underwent the second IVF cycle 1–2 months after the first one, we assumed that the weight change in this time period would not affect the outcome. The strengths of our study are the length of follow-up and the assessment of IVF outcomes in patients with a previous BS for up to 3 years. In addition, as treatments are funded by the National Health Insurance Law, with almost no limit for the number of cycles and only negligible self-co-payment, patients were followed up for up to 36 months.

Obesity is a significant global health issue, and its prevalence has nearly tripled since 1975 [ 1 ]. For women in the USA, the prevalence of overall obesity and class III obesity (body mass index [BMI] 40–49.9 kg/m 2 ) has increased linearly over the last decade [ 2 ]. Obesity may result in several adverse health concerns, including infertility. While the exact mechanisms are still unclear, it is supposed that free fatty acids and leptin associated with obesity might negatively affect female fertility and impair ovarian and endometrial function, causing both impaired oocyte maturation and endothelial dysfunction [ 3 , 4 ]. Previous studies have shown decreased pregnancy and live birth rates in women with class II (BMI 35–39.9 kg/m 2 ) and class III obesity compared to those with normal BMI [ 5 , 6 ]. Weight loss before fertility treatment may improve conception and live birth rates by reducing perinatal morbidity and mortality [ 7 ]. One treatment option to achieve significant weight loss is bariatric surgery (BS) [ 8 ]. BS is currently the most effective long-term weight loss approach for females of reproductive age [ 9 ]. The impact of weight reduction through BS on fertility treatment success rates is still being studied [ 9 – 11 ]. Previous data have suggested a positive influence of BS on in vitro fertilization (IVF) outcomes. Women undergoing BS before IVF needed fewer gonadotropins [ 8 , 12 ] and had an increased number of quality oocytes, higher fertilization rates, and more top-quality embryos than those undergoing IVF treatment before surgery. Moreover, in the cycle following BS, they had significantly higher pregnancy and live birth rates [ 8 ]. However, studies to date that evaluated pregnancy outcomes following BS usually looked at the outcomes of the first IVF cycle following the operation and did not explore the time to pregnancy after cumulative IVF cycles among these women [ 8 , 12 – 14 ]. Another concern is that weight regain after BS is an emerging clinical problem [ 15 ]. Some degree of weight regain is common after patients reach their nadir weight; however, 20–35% of patients struggle with weight increase [ 16 , 17 ]. The primary endpoint of this study was to estimate the time to pregnancy and live births in women with a history of BS who underwent IVF treatment. As a secondary study endpoint, we assessed the effect of weight regain on conception and live birth rates.

The authors have none to declare.

This study was not supported by any sponsor or funder.

Data were reviewed for all patients with previous BS who underwent IVF treatment at a single tertiary university-affiliated center between 2013 and 2022. Only treatment and time to pregnancy following BS were analyzed. The women underwent controlled ovarian stimulation with either a long GnRH agonist (Decapeptyl ® 0.1 mg, Ferring, Saint-Prex, Switzerland) or a GnRH antagonist protocol (Cetrotide 0.25 μg, Merck KGaA, Darmstadt, Germany). Recombinant hCG (Ovitrelle; Merck S.A., Fenil-sur-Corsier, Switzerland) was administered to induce an LH surge when at least two follicles of the cohort reached a mean diameter of ≥18 mm. Fresh embryo transfer was performed on days 2 or 3. We excluded patients who underwent IVF due to social oocyte cryopreservation, women who underwent IVF for the preimplantation genetic testing for monogenic disorders (PGT-M), and those with no normal embryos for transfer. The follow-up time was up to 36 months after the first IVF treatment. Women who did not conceive within 36 months were excluded. Clinical information, including demographics and IVF outcomes, was obtained from patients’ electronic medical records. Treatment outcomes were defined as the implantation, clinical pregnancy, and live birth rates. Positive β-hCG was defined as β-hCG >25 IU 14 days after embryo transfer. Clinical pregnancy was defined as an intrauterine gestational sac with or without fetal heartbeat 4 weeks after transfer. The live birth rate was defined as delivery after 24 weeks of gestation. For each endpoint, the total time in months was calculated. Categorical variables were summarized as frequencies and percentages. Continuous variables are reported as mean (SD) and median (IQR) for ease of reading. Patients’ baseline characteristics and first treatment data were compared using the Mann-Whitney test (continuous and ordinal variables) or χ 2 test (categorical variables). The reverse censoring method was used to evaluate the length of the follow-up. Kaplan-Meier curves were used to describe implantation, clinical pregnancy, and live births during the follow-up period. The delta between BMI during the first IVF treatment and the nadir BMI following surgery was divided into two categories to evaluate the effect of weight regain on IVF outcomes. As up to 35% of patients regained weight following BS, we used the second tertile value (66%) rounded to the nearest integer as the cutoff value. Kaplan-Meier curves and log-rank tests were used to compare study outcomes between the two categories. Univariate Cox regression was used to evaluate the crude hazard ratio, whereas multivariate Cox regression was applied to control for potential confounders. All statistical tests were two-sided. Statistical significance was set at p < 0.05. All statistical analyses were performed using the SPSS software (IBM SPSS Statistics for Windows, version 28, Armonk, NY, USA, 2021).

This study protocol was reviewed and approved by the Sheba Medical Center’s Ethical Review Board (Ethical Approval No. 7608-20). This retrospective study did not require patient consent in accordance with local or national guidelines.

B.Z.T. and M.I.: substantial contributions to the conception of the work and drafting of the manuscript. T.Z.B.: substantial contributions to the interpretation of data. G.L. and R.O.: revising it critically for important intellectual content. R.M.: substantial contributions to the design of the work and revising it critically for important intellectual content.