The role of bariatric surgery in enhancing IVF outcomes for obese women: A systematic review protocol

*Corresponding author: Sholen Acharya Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. The role of bariatric surgery in enhancing IVF outcomes for obese women: A systematic review protocol Sholen Acharya 1, * and Deepak Rath 2 1 Department of Reproductive Medicine and Surgery, Government Medical College, Thiruvananthapuram, Kerala, India. 2 Department of Rheumatology, SUM Ultimate Medicare, Bhubaneswar, Odisha, India. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 118-124 Publication history: Received on 21 January 2025; revised on 01 March 2025; accepted on 04 March 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.21.3.0254 Abstract This systematic review protocol lays the foundation for the systematic review, which aims to assess the impact of bariatric surgery on IVF outcomes, particularly cumulative live birth rates, in obese women. Obesity contributes to infertility through hormonal imbalances, metabolic dysfunctions, and ovulatory irregularities. Bariatric surgery has been proposed to enhance reproductive outcomes by inducing significant weight loss. However, in those who require early IVF, risks may outweigh benefits, as the waiting period between surgery and IVF may affect their ovarian reserve, reducing success rates. The study protocol follows PRISMA guidelines and will include randomised controlled trials and observational studies evaluating IVF success post-surgery. Primary outcomes that will be studied will include cumulative live birth rates, while secondary outcomes examine pregnancy rates, gonadotropin doses, cycle cancellation, ovarian reserve markers, and implantation rates. The summary statistics represented by odds ratio for the metaanalysis will be calculated using a random-effects model. Heterogeneity will be assessed using I2 statistics, and subgroup analyses may be done if more low to moderate risk-of-bias studies are found. Findings from this study will provide evidence-based insights into the effectiveness of bariatric surgery as a pre-IVF intervention, aiding clinicians in optimising fertility treatment strategies for obese women. Keywords: Bariatric Surgery; In-Vitro Fertilization (IVF); Obesity; Infertility; Live Birth Rate 1. Introduction Obesity among women of reproductive age has become a global health concern. Obesity has been defined by the World Health Organization (WHO) as having a body mass index (BMI) of 30 kg/m² or greater, and several metabolic disorders like type 2 diabetes, hypertension and polycystic ovarian syndrome (PCOS) are associated with it [1]. The rising prevalence of obesity is accompanied by a notable increase in infertility, with approximately 12–15% of couples experiencing difficulty conceiving globally [2]. Women who are obese are more likely to experience infertility due to a combination of hormonal imbalances, altered ovarian function, and irregular menstrual cycles [3]. Furthermore, obesity is linked to a higher incidence of anovulation, impaired embryo quality, and reduced success rates in assisted reproductive technologies (ART) like in-vitro fertilisation (IVF) [4], [5]. Bariatric surgery has become an increasingly common intervention for morbid obesity, particularly for individuals with associated metabolic disorders or infertility. Bariatric surgery aims to induce significant weight loss through various procedures such as gastric bypass (Roux-en-Y), sleeve gastrectomy, and adjustable gastric banding [6]. These procedures result in reductions in food intake and absorption, leading to weight loss, improved metabolic function, and, in many cases, resolution of obesity-related comorbidities like PCOS [7] and diabetes [8]. Studies have shown that weight loss following bariatric surgery can lead to improvements in ovulatory function, hormone levels, and menstrual regularity, which may improve fertility outcomes [9]. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 118-124 119 In particular, bariatric surgery is thought to enhance fertility outcomes by addressing several factors that impair reproductive function in obese women. For instance, weight loss may improve insulin sensitivity and reduce levels of inflammatory cytokines [10] that impair ovulation [11]. Moreover, bariatric surgery may improve ovarian reserve markers such as Anti-Müllerian hormone (AMH) and antral follicle count (AFC), which are critical indicators of fertility potential [12]. There is also emerging evidence that bariatric surgery before IVF may increase the chances of successful live birth outcomes by improving both ovarian response to stimulation and embryo quality [13]. However, bariatric surgery is not without risks, and one key concern is the recommended waiting period between surgery and conception. Due to potential nutritional deficiencies and malabsorption associated with bariatric surgery, women are generally advised to wait at least 12 months before attempting conception [14]. This waiting period is intended to allow time for nutritional stabilization, as deficiencies in vitamins and minerals, particularly folate, iron, and vitamin B12, can negatively affect fertility and pregnancy outcomes [15]. Yet, there remains a debate about the optimal timing of IVF following bariatric surgery [16],[17]. For women who have undergone surgery, it is crucial to determine whether the benefits of weight loss outweigh the risks of delayed conception, particularly in relation to ovarian reserve and IVF success rates. Several studies have attempted to investigate the impact of bariatric surgery on fertility outcomes in obese women undergoing IVF. While some studies suggest improved pregnancy and live birth rates following bariatric surgery, others highlight potential complications, including a prolonged time to conceive [18]. Therefore, there is a need for a systematic review to comprehensively evaluate the existing evidence on bariatric surgery and its impact on IVF outcomes, particularly live birth rates. This review aims to clarify whether undergoing bariatric surgery prior to IVF improves the chances of live birth in obese women of reproductive age. Objective Review Question: Does undergoing bariatric surgery before in-vitro fertilisation (IVF) improve the chances of live birth in obese, infertile women of reproductive age undergoing IVF? The objective of this review is to evaluate the effect of bariatric surgery on IVF outcomes when performed before IVF in terms of cumulative live birth rates, pregnancy rates, and related reproductive outcomes in obese infertile women of reproductive age. 2. Methodology The study protocol is developed and reported based on the Preferred Reporting Items for Systematic Reviews and MetaAnalysis (PRISMA) Guidelines [19] and has been registered with the International Prospective Register of Systematic Review (PROSPERO) with ID CRD42024562399. 2.1. Searching and screening 2.1.1. Searches The databases PubMed/MEDLINE, PMC (PubMed Central), Google Scholar, Scopus, Cochrane Library, Directory of Open Access Journals (DOAJ) and Clinical Trials Registry (www.ClinicalTrials.gov) will be searched independently by two investigators. The search will use the keywords “bariatric surgery” and “in-vitro fertilisation”. Only English language publications, including those translated into English, will be considered, with no restrictions on the publication period. Unpublished studies will not be sought for review. The searches will be re-run before the final analysis to include any relevant moderate to high-quality studies that become available. 2.1.2. Study design Original English-language articles reporting on in-vitro fertilization (IVF) outcomes after bariatric surgery will be considered for inclusion. This includes both randomized controlled trials and non-randomized studies such as case series, cohort studies, case-control studies, and cross-sectional studies for qualitative review. For quantitative synthesis of results, only randomized trials and non-randomized controlled studies, such as cohort and case-control studies with a moderate to low risk of bias, will be considered, based on the study population and outcome measures relevant to this review. Conference abstracts with a relevant study population and study design will be discussed qualitatively only. A risk of bias assessment will not be performed for abstracts due to the inadequate information they provide. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 118-124 120 2.2. Eligibility criteria This review will systematically discuss studies exploring the relationship between bariatric surgery and IVF outcomes. When similar studies are available regarding patient populations and outcomes, they may be pooled to generate an effect estimate. This will help determine whether undergoing bariatric surgery prior to IVF improves its outcomes. 2.2.1. Population Inclusion Criteria: This review will include all studies involving women of reproductive age (18-45 years) diagnosed with obesity according to WHO criteria [20], have infertility and have undergone in-vitro fertilisation to achieve pregnancy. Exclusion Criteria: Studies involving obese men with infertility, obese women with infertility who are not planning to undergo IVF, or those receiving fertility treatments other than IVF will be excluded. 2.2.2. Intervention(s) or exposure(s) Studies with intervention as bariatric surgery before IVF, will be included. The common types of bariatric surgeries are gastric bypass (Roux-en-Y gastric bypass), sleeve gastrectomy and adjustable gastric banding. • Gastric bypass (Roux-en-Y gastric bypass): A small pouch is created which is directly connected to the intestine, bypassing a large portion of the stomach; this reduces food absorption, leading to malnutrition and weight loss • Sleeve gastrectomy: Around 70-80% of the stomach is removed due to which hunger hormone ghrelin is reduced and reduces the amount of food intake • Adjustable gastric banding: A band is placed at the upper part of the stomach, leading to a reduction in the size of the stomach 2.2.3. Comparator(s) or control(s) Inclusion: The comparator arm must consist of obese women of reproductive age who are diagnosed with infertility and undergoing in-vitro fertilisation (IVF) without prior bariatric surgery. Exclusion: Non-obese women of reproductive age who are diagnosed with infertility and undergoing IVF will not be considered as controls for this review. 2.2.4. Outcomes Primary outcome The primary outcome of this review is to quantify the difference in the cumulative live birth rate in terms of the odds ratio between those who undergo bariatric surgery before IVF and those who do not undergo bariatric surgery before IVF. Therefore, all studies reporting cumulative live birth rates will be ideal for inclusion and can be used for quantitative synthesis. The cumulative live birth rate is defined by the number of viable pregnancies (≥24 weeks) delivered after fresh and frozen embryo transfers, with embryos retrieved from single oocyte retrieval [21]. If cumulative live birth rate data is unavailable, the live birth rate will be considered as the primary outcome. The live birth rate is defined by the number of viable pregnancies delivered after the first embryo transfer, fresh or frozen, divided by the number of egg retrievals [21]. Secondary outcomes Studies reporting outcomes like clinical pregnancy rate, pregnancy loss rate, time to live birth (provided in prospective studies), gonadotropin doses, cycle cancellation rate, number of mature oocytes, fertilization rate, implantation rate, ovarian hyperstimulation risk, etc will be taken for qualitative analysis. Table 1 Definitions of Secondary Outcomes Secondary outcome Defined in studies Pregnancy Rate Confirmed pregnancy (rise in beta-hCG or gestational sac visible on ultrasound). Pregnancy Loss Rate Includes biochemical losses, miscarriages, and ectopic pregnancies. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 118-124 121 Time to Live Birth Time from randomization or bariatric surgery to live birth (prospective study) Gonadotropin Doses Standardized mean difference for doses used Cycle Cancellation Rate Number of cancelled IVF cycles divided by total number of cycles Number of Mature Oocytes Count of metaphase II oocytes Ovarian Hyperstimulation Syndrome (OHSS) Risk Comparison of OHSS cases between groups 2.3. Data collection (selection and coding) 2.3.1. Study selection All the articles after systematic search, will be entered into the Rayyan software [22] where duplicates will be removed. The investigators will be provided training on using Rayyan for the purpose of screening articles. Two reviewers will independently screen the title and abstract of papers and record their decisions in Rayyan, along with the reason for exclusion. Both reviewers will be blinded to each other’s decisions during the screening process. Any difference in opinion will be resolved using discussion between the investigators. 2.3.2. Data extraction The data extraction form will be created in Google Docs and two investigators (SA and DR) will independently extract data and enter them into this spreadsheet. The following data from the studies will be systematically extracted • Study Characteristics: Author, year, country, study design, objective, population, inclusion/exclusion criteria, intervention, comparator, primary outcome, secondary outcomes. • Population Characteristics of Both Arms: Age, BMI, type of bariatric surgery, ovarian reserve markers (AntiMullerian Hormone, Antral Follicle Count), and cause of infertility. • Outcome Characteristics for Both Arms: Doses of gonadotropins, number of cancelled cycles, number of mature oocytes, cases of OHSS, number of pregnancies, number of pregnancy losses, number of live births, time to live birth, odds ratio with 95% confidence interval (both adjusted and unadjusted). All disagreements will be resolved with discussion. 2.4. Risk of bias (quality) assessment The final studies included in the review will be assessed for risk of bias using two tools: ROB 2 (Risk of Bias tool developed by the Cochrane Collaboration) for randomized studies [23] and ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) for non-randomized controlled studies [24]. ROB 2 assesses five domains: randomization process, deviations from intended interventions, missing data, measurement of outcomes, selection of reported results ROBINS-I evaluates seven domains: confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, measurement of outcomes, selection of reported results For studies without a control group, risk of bias assessment will not be conducted, as it does not provide a valuable effect estimate. Two reviewers will independently perform the risk of bias assessments, blinded to each other’s evaluations. Disagreements will be resolved through discussion among all authors. The risk of bias assessments will be presented using summary plots and traffic light plots created with the {robvis} package in R (Version 4.4.1). 2.5. Data synthesis Data analysis will be conducted using the {meta} and {metafor} packages in R (Version 4.4.1) [25]. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 118-124 122 2.5.1. Quantitative Synthesis (Meta-analysis) Studies with low to moderate risk of bias and similar populations in both intervention and control groups will be considered for quantitative synthesis. Since the primary outcome is dichotomous, the measure of effect is the odds ratio with a 95% confidence interval (CI). Pooling of this effect estimate will be done using the random effects model due to considerable between-study heterogeneity [26], and the summary estimate is represented as an odds ratio with 95% CI. The generic inverse variance method will be employed for pooling. For non-randomized studies, adjusted odds ratios will be prioritized. In their absence, crude or unadjusted odds ratios may be used, acknowledging the potential confounding associated with such analyses. If a sufficient number of low to moderate-risk of bias studies are available, secondary outcomes may be pooled. For continuous outcomes, the effect size will be expressed using the corrected standardized mean difference (Hedges' g) with a 95% confidence interval. If the standardized mean difference(SMD) is not provided, the mean and standard deviation of both groups will be used to calculate it. The SMD will be pooled using a random effects model. The pooling method for SMD will be the generic inverse variance method. All the results will be presented in Forest plots. 2.5.2. Heterogeneity Between-study heterogeneity will be assessed using the Cochran Q test and I2 statistics [27]. 2.5.3. Sensitivity analysis/ Subgroup analysis It will be conducted using studies assessed as having a low risk of bias. If I2 exceeds 50%, outlier and influence analysis will be conducted using the Baujat plot. Meta-analysis may be repeated after removing outliers. Subgroup analysis based on BMI classification before surgery and type of bariatric surgery may be considered if the number of included studies is greater than 20. 2.5.4. Publication bias It will be assessed by plotting the effect sizes of primary outcomes against study precision (inverse of standard error) to generate a funnel plot. The asymmetry of the funnel plot will be evaluated using Peters’ regression test. If publication bias is detected, the Duval and Tweedie trim and fill method will be applied to generate a corrected pooled effect estimate. 3. Discussion This systematic review protocol aims to evaluate the impact of bariatric surgery on in-vitro fertilization (IVF) outcomes in obese, infertile women of reproductive age. Given the rising global prevalence of obesity and its well-established role in reducing fertility, particularly in women with obesity-related infertility, bariatric surgery presents a potential intervention to improve reproductive outcomes. 3.1. Live Birth Rate as Primary Outcome Though several studies have highlighted the role of bariatric surgery in improving fertility outcomes in obese women, its role in specifically improving the live birth rate after in-vitro fertilisation might not have been reported in several studies. The ultimate goal of reproductive interventions is to have a live birth. Several obese women may require early IVF, and performing a bariatric surgery may delay their chances of conception, which may have detrimental effects on the outcomes. The best evidence to analyse these effects are randomised controlled trials, which may be difficult to conduct owing to the heterogeneity in patient characteristics and procedures involved. As a result, much of the evidence included in this review will likely come from observational studies, which, while valuable, may not provide the same level of robust evidence as RCTs. 3.2. Study Quality and Limitations The studies included in this review are likely to vary in quality, as both RCTs and observational studies will be considered. While RCTs are ideal for establishing causal relationships, they are difficult to conduct in the context of bariatric surgery due to ethical and logistical challenges. As a result, much of the evidence is derived from cohort and case-control studies, which are prone to confounding factors and biases. To enhance the validity of the review’s findings, only studies with a low to moderate risk of bias will be included in the quantitative synthesis. A risk of bias assessment will help identify potential weaknesses in the studies and aid in interpreting the results. Given the diversity in study populations (e.g., age, BMI, comorbidities), types of bariatric procedures, IVF protocols, and the timing of surgery in relation to IVF, there may be significant variability in the reported outcomes. To account for this heterogeneity, statistical methods such as random-effects models and sensitivity analyses will be used. Furthermore, subgroup World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 118-124 123 analyses will be conducted based on different bariatric surgery types and BMI categories to assess how these factors influence IVF outcomes. 3.3. Implications for Clinical Practice This systematic review will provide valuable insights into the role of bariatric surgery in improving IVF outcomes in obese women, which could inform clinical decision-making. If bariatric surgery is found to significantly improve IVF success rates, it could be integrated into fertility treatment plans for obese women. However, the review will also highlight the importance of individualized care, especially in terms of the timing of IVF and nutritional management post-surgery. Clinicians will need to balance the benefits of weight loss and metabolic improvements with the potential risks of malnutrition and delayed conception. Moreover, the review will help refine guidelines on the optimal timing of IVF after bariatric surgery, considering both the risks of early conception and the potential for diminished ovarian reserve with longer delays. These findings may also lead to a better understanding of how bariatric surgery affects IVF success across different patient populations, ultimately contributing to more personalized treatment strategies. 4. Conclusion The role of bariatric surgery in improving IVF outcomes for obese women is an important area of research. While preliminary evidence suggests that bariatric surgery may improve ovarian function, ovulatory regularity, and overall fertility outcomes, the optimal timing for IVF and the specific impact of different surgical procedures require further exploration. This systematic review aims to provide a comprehensive evaluation of the available evidence and offer guidance on the clinical management of obese women seeking IVF. Through careful synthesis of the available data, this review will help clarify the role of bariatric surgery in improving IVF success rates and guide future research in this critical area of reproductive medicine. Compliance with ethical standards Disclosure of conflict of interest No conflict of interest to be disclosed. References [1] F. C. 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