Abstract
Background:
The prevalence of obesity is increasing worldwide, with several consequences, including reduced fertility in both men and women. One of the ways to reduce weight is bariatric surgery. The aim of this systematic review and meta-analysis study was to evaluate the effectiveness of bariatric surgery on weight loss and subsequent improvement of fertility in obese infertile women.
Methods:
Several databases were searched using MESH terms to investigate the studies that evaluated the fertility rates after bariatric surgery in infertile obese women. Related data were obtained and analyzed using Stata software with a P-value ≤0.05, which was considered as significant.
Results:
Of the 283 articles related to the purpose of this study, 9 articles, including 231 obese infertile women, were included in the study. BMI before surgery was 42.2 [95% CI= 39.2–45.2] and BMI after surgery was 31.9 (95% CI= 28.9–34.8), which shows the significance of weight loss after bariatric surgery. Conception rate after bariatric surgery weight loss was increased and was 67% (95% CI= 47–87%, P-value <0.05).
Conclusions:
Bariatric surgery had a significant effect on the reduction of BMI and subsequent significant improvement of fertility in obese infertile women.
Keywords: bariatric surgery, infertility, meta-analysis, obesity
Introduction
Highlights
The prevalence of obesity is one of the increasing problems.
Most of obese people are women of reproductive age.
Obesity disrupts reproductive processes.
Bariatric surgery have a significant effect on reducing BMI.
Bariatric surgery have a significant effect on improving fertility.
The prevalence of obesity is a widespread and growing problem1. The statistics of this problem as one of the health issues in 2016 reached 650 million people, which is 13% of the world’s population2,3. Approximately 80% of obese people are women, most of whom are of reproductive age3. Studies show a link between obesity and infertility, suggesting that fertility increases with weight loss in obese women1. Obesity, as one of the risk factors during pregnancy, has adverse consequences for both mother and fetus, including difficult pregnancy, miscarriage, and congenital abnormalities4. Obesity disrupts reproductive processes and characteristics by disrupting the normal hormone levels5. Therefore, weight loss in obese women regulates menstrual and ovulatory cycles and increases the likelihood of fertility6. Drug treatment for infertility is usually not prescribed because of the side effects of some medications7. Despite the conflicting results of some studies on the positive effect of weight loss on improving fertility8,9, especially through surgery, most studies confirm this relationship10. In obese patients who have failed drug treatment, surgery should be considered as an obesity treatment1. Bariatric surgery is usually considered in people with severe obesity who have not been treated by other methods, such as medical therapy and lifestyle changes11. The most effective long-term weight loss treatment is bariatric surgery. It should be noted that more than half of these surgeries are performed on women who are of reproductive age12. Since its introduction (1960s), bariatric surgery has been gradually become accepted and has become the main method of obesity treatment11. Bariatric surgery includes a group of surgeries on the stomach or intestines11. This type of surgery, as the most effective treatment method for morbid obesity, is divided into two categories: malabsorption and restriction5. The most commonly used surgical procedures are already Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding(AGB)11. SG, gastric bypass, and laparoscopic AGB are some of the most commonly used procedures in the world5.
According to previous studies bariatric surgery can improve fertility but the rate of increase in fertility after bariatric surgery in obese infertile women has not been determined by a comprehensive study. This study was conducted to examine the complications of obesity in infertile women and the beneficial effects of bariatric surgery on weight loss and fertility.
Method
Study protocol
This study was conducted using PRISMA (Preferred Reports for Systematic Reviews and Meta-Analyses) to determine the effect of bariatric surgery on infertility in obese women.
Search strategy
The databases Web of Science (ISI), PubMed, Cochrane Library, Wiley Online Library, CINAHL, EMBASE, Scopus, Springer, Science Direct, and Google Scholar search engines were searched without a time limit to find the relevant studies. The MeSH keywords used included bariatric surgery, obesity, Roux-en-Y gastric bypass, sleeve gastrectomy, adjustable gastric banding, one anastomosis gastric bypass (OAGB), and infertility. These steps were performed and reviewed by two of the authors.
Inclusion and exclusion criteria
Inclusion criteria were studies evaluated the changes in fertility rate after bariatric surgery. This review excluded nonhuman and non-English studies, as well as case reports, case collections, letters, articles with insufficient data, studies did not show the changes in the rate of conception after surgery and cases for which full text was not available.
Quality assessment
In this phase of the study, all collected studies were simultaneously and independently assessed by two authors using the modified Newcastle–Ottawa Scale (NOS), and finally, those articles that received an acceptable score of 6 or more were included in the study.
Study selection
To perform an initial screening to select relevant articles, endnote software was used to store and remove duplicate articles. The titles and abstracts of the articles were then scanned. The next step was to examine the full text of the articles.
Data extraction
Based on the information extraction table, the data was extracted by the researchers. The extracted data included the following: author name and year of article publication, country name, and study type, number of infertile women, mean age, presurgery BMI, postsurgery BMI, follow-up, (month), live birth rate (LBR), conception, and type of surgery. These data were then stored using an Excel program.
Statistical analysis
In this study, descriptive statistics (mean, median, and SD for continuous variables and frequency and percentage for categorical variables) were used. A weighted mean was used to estimate the pooled mean and 95% CI of BMI. The Metaprop command in Stata software was used to determine the incidence of conception among infertile women. Random-effects meta-analysis was used in this study. Heterogeneity among included studies was assessed using I 2 and Q statistics. A sensitivity analysis was performed to determine the robustness of the results. At each stage, one study was omitted and the results were compared with the full analysis. Stata software (version 14.2) was used for all statistical analyses. In addition, a funnel plot was used to assess publication bias. In addition, all comparisons were two-tailed with a threshold P-value ≤0.05 for statistical significance.
Results
Study characteristics and methodological quality
After a complete review of the collected articles and removing 72 duplicates items and reviewing 87 abstracts and 124 complete articles finally, of the 283 articles collected, 9 articles including 231 infertile obese women were included in the meta-analysis (Fig. 1, and Table 1).
Figure 1.
PRISMA flowchart.
Table 1.
Data obtained from a review of studies on the impact of bariatric surgery on infertility.
| Author, year (reference) | Country | Number of infertile women | Mean age (SD) | BMI before surgery | BMI after surgery | Follow-up (month) | Conception | LBR | Time to pregnancy (month) | Type of surgery |
|---|---|---|---|---|---|---|---|---|---|---|
| Jamal, 201213 | US | 6 PCOS | – | – | – | 46.7 | 6 | Six (5 spontaneous + 1 IUI) | Within 3 years | RYGB |
| Ahmed, 201714 | Iraq | 16 (8 PCOS and 8 non PCOS) | 30.2 (4.04) | 46 (7.8) | 35.3 (4) | 48 | 14 | 14 (spontaneous pregnancy) | 3.4 (0.3) | LSG |
| Milone, 201715 | Italy | 40 with a history of ART failure | 31.4 (4.7) | 40.7 (2) | 35 (2.6) | 15 | 14 ART | – | LSG | |
| Khazraei, 201716 | Iran | 15 | – | – | – | 20 | 7 | Five (spontaneous) | – | LSG |
| Menke, 201917 | US | 52 (27 PCOS and 25 non PCOS) | – | – | – | 78 | 22 | 21 (spontaneous pregnancy) | – | 33 RYGB and 16 LAB and 3 other |
| Nayak, 202018 | India | 28 (17 PCOS & 11 non PCOS) | 29.56 (4.2) | 42 (4.6) | 30.14(3.9) | 12 | 18 | 18 (14 spontaneous, 4 ICSI) | – | LSG |
| Öner, 20234 | Turkey | 23 (PCOS and non PCOS) | 31.26 (5.06) | 45.04(3.4) | 28.6 (3.1) | 12 | 21 | 15 (10 spontaneous, 3 IVF, 2 S+IVF) | 25.6 (4.7) | LSG |
| Abbas, 202319 | Pakistan | 56 PCOS | 30.8 (4.2) | 45.2 (5.6) | 27.8 (4.2) | 34 | 53 | 47 (spontaneous) | 34 (26) | Not sustained |
The effect of bariatric surgery on obese women BMI
The BMI of infertile patients before and after surgery was 42.2 (95% CI= 39.2–45.2) and 31.9 (95% CI= 28.9–34.8), respectively (Figs. 2, 3).
Figure 2.
BMI of infertile patients before bariatric surgery.
Figure 3.
BMI of infertile patients after bariatric surgery.
The analysis shows that there is a significant difference in the BMI of patients before and after surgery.
The effect of bariatric surgery on infertility and subgroup analysis
The overall pooled estimate of fertility after bariatric surgery was 67% (95% CI= 47–87%, P-value <0.05) (Fig. 4).
Figure 4.
Meta-analysis of studies on the impact of bariatric surgery on infertility.
Heterogeneity was high in this meta-analysis (I 2=93.9%; P-value=0.00), and the subgroup analysis was checked according to the type of surgery (Fig. 5). Due to the limitations of the studies and the lack of common data in this area, it was not possible to accurately determine the cause of heterogeneity using a subgroup of analysis. The time of conception from surgery was different in the included articles from 12 to 78 months. The average time to conception was 35.8 months.
Figure 5.
Subgroup analysis in a meta-analysis of studies on the impact of bariatric surgery on infertility.
Sensitivity analysis
For sensitivity analysis, reanalysis was performed after excluding each study in the remaining studies, and according to the evaluation, our findings were not affected by the excluded studies Fig. 6.
Figure 6.
Sensitivity analysis in a meta-analysis of studies on the impact of bariatric surgery on infertility.
Publication bias
According to Egger’s test and funnel design, no bias was found among the articles analyzed (P>0.05) Fig. 7.
Figure 7.
Publication bias in a meta-analysis the impact of the bariatric surgery on infertility.
Discussion
According to the results of the meta-analysis, there is a direct relationship between obesity and infertility. In addition to obesity, PCOS is one of the major factors that increase the likelihood of infertility in overweight women. The causes of the effect of obesity on infertility have been explained. For example, the fat cells of obese women produce a lot of leptin, which can alter the menstrual cycle by disrupting the hormonal balance and lead to infertility5. Therefore, the relationship between obesity and infertility is strong, and weight loss plays an effective role in the treatment of infertility in obese women1. Bariatric surgery has been shown to play an effective role in the treatment of infertility20. One of the most effective ways to treat obesity is bariatric surgery, which improves libido and sexual activity by improving PCOS symptoms (hormonal changes, lack of ovulation, and hirsutism)4. According to the analysis of nine articles reviewed in this study, bariatric surgery leads to weight loss and improvement of infertility in women by 67%. In the study conducted by Christinajois et al.13 to investigate LSG in obese women (40 people), the results showed that the fertility rate after surgery was 43.75%.
The results of a meta-analysis study showed the positive effect of bariatric surgery on women with PCOS and obesity, with a significant reduction in the prevalence of PCOS, menstrual irregularity, and hirsutism 1 year after surgery14. In another study, it was reported that the percentage of fertility in infertile obese women with PCOS reached 100% (six patients) after bariatric surgery15. BMI delays conception in a dose-dependent manner in women16,17. Studies have shown that high BMI can cause ovulation failure, followed by menstrual irregularity and impaired oocyte development, and its direct effect on the endometrium has been demonstrated18. Several studies report that reducing BMI after bariatric surgery plays an effective role in reducing the risk of delivering a macrosomic baby19. Musella and colleagues (2012) found that BMI and degree of weight loss after surgery were notable predictors of pregnancy1. These results are supported by the present study.
Qurashi et al. evaluated the effects of bariatric surgery on both genders and demonstrated improvement in erectile function scores, increased total and free testosterone, decreased estradiol and increased sperm morphology in males. They demonstrated an increase in sex hormone levels (FSH, LH, and SHBG) and sexual function in both sexes, and decreased total and free testosterone and estradiol in females, but menstrual irregularities, total sperm count, semen volume, sperm motility, and concentration did not significantly changed at 12 months follow-up21. According to previous studies, bariatric surgery improves the rate of fertility in women by modulating the hypothalamic–pituitary–ovarian (HPO) axis with changes in ovarian hormone levels such as estradiol and progesterone. As BMI decreases after bariatric surgery levels of leptin and two adipokines, leptin and adiponectin will change that may affect the fertility22. Studies have also shown another potential reason of increase in fertility after bariatric surgery is increase in antimullerian hormone (AMH) levels by weight loss in patients with and without PCOS23. Another studies support that after bariatric surgery and BMI loss, sexual function will improve in women who do not have pelvic floor disorders24. Although bariatric surgery can increase fertility, but time-to-conception interval must be considered and special care is needed before, during and after pregnancy11,25. Despite using supplementations the rate of micronutrient deficiency in post bariatric surgery pregnant women is high that shows the need for proper monitoring of nutrition by a multidisciplinary team to maintain the health of mother and fetus26. Potential effects of bariatric surgery on pregnancy is reducing the risk of preeclampsia, gestational diabetes or impaired fasting glucose and large-for-gestational-age neonates but increases the risk of small-for-gestational-age (SGA) neonates27. The rates of gestational diabetes mellitus, gestational hypertension, and cesarean section can reduce significantly after bariatric surgeries28. Considering the present meta-analysis, the heterogeneity was high, but there were few similar articles, the source of heterogeneity was unclear, and the only subgroup investigated was the type of surgery, the result of this subgroup is not valuable due to the limitation of the studies in each subgroup and more comprehensive studies are needed to find the procedure of choice. Biases present in the included studies or discrepancies in study designs is the reason of limitation of the studies in each subgroup.
Conclusion
Bariatric surgery, by reducing the weight of obese patients, effectively leads to restoration of the menstrual cycle and improvement of hyperandrogenism as well as its clinical manifestations and subsequently causes ovulation and normal pregnancy in pregnant patients. Therefore, bariatric surgery may be an appropriate treatment option for obese infertile patients, especially if they have not been treated with medications and lifestyle changes. Further studies are recommended.
Ethical approval
Kermanshah University of Medical Sciences Research Committee.
Consent
This is a meta-analysis study and we did not have access to patients.
Source of funding
There related data was declared.
Author contribution
Z.T., P.G.H., and M.O.: acquired the data; Z.T.: analyzed and interpreted data; B.M., Z.T., and P.G.H.: drafted the manuscript; B.M. and M.O.: critically revised the manuscript; B.M.: supervised the study. All authors have read and approved the manuscript.
Conflicts of interest disclosure
The authors declare no conflicts of interest.
Guarantor
Zeinab Tardeh.
Data availability statement
Datasets generated during and analyzed during the current study are publicly available.
Provenance and peer review
The paper is not commissioned, externally peer-reviewed.
Acknowledgements
The authors sincerely thanks Kermanshah University of Medical Sciences.
Footnotes
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Published online 23 October 2024
Contributor Information
Behnam R. Makhsosi, Email: behnam.makhsosi@gmail.com.
Pourya Ghobadi, Email: Pourya.ghobadi@yahoo.com.
Masoumeh Otaghi, Email: otaghi-m@gmail.com.
Zeinab Tardeh, Email: z.tardeh@gmail.com.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Datasets generated during and analyzed during the current study are publicly available.