|Year : 2017 | Volume
| Issue : 4 | Page : 210-215
Effect of weight loss on In Vitro fertilization treatment outcome
Jing-Yan Song1, Shan Xiang2, Zhen-Gao Sun3
1 Department of Gynecology of Traditional Chinese Medicine, The First Clinical College, Shandong University of Traditional Chinese Medicine; Reproductive Medicine Center of Integration of Traditional and Western Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, China
2 Department of Gynecology of Traditional Chinese Medicine, The First Clinical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, China
3 Reproductive Medicine Center of Integration of Traditional and Western Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan , Shandong 250011, China
|Date of Submission||20-Oct-2017|
|Date of Web Publication||7-Feb-2018|
No. 42, Wen Hua Xi Road, Lixia District, Jinan 250011
Source of Support: None, Conflict of Interest: None
Background: To assess the effect of weight loss in overweight and/or obese women on the in vitro fertilization (IVF) treatment outcome before IVF cycles by a systematic review and meta-analysis of clinical trials.
Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies were conducted. Systematic literature searches were conducted, and all randomized trials that evaluated the impact of weight loss in IVF treatment cycles were included in the study. Study selection, quality estimation, and data extractions were performed independently and in duplicate.
Results: A total of 924 patients were enrolled in seven studies; the effects of weight loss on the IVF treatment outcome before the IVF treatment cycle were assessed. The clinical pregnancy rate (risk ratio [RR]: 1.61, 95% confidence interval [CI]: 1.15–2.27), miscarriage rate (RR: 0.56, 95% CI: 0.34–0.93), and live birth rate (RR: 1.86, 95% CI: 1.41–2.45) had a statistically significant difference between the intervention and control group. No significant differences were observed in the number of oocytes retrieved (weighted mean difference [WMD]: 0.84, 95% CI: −0.12–1.79), gonadotropin consumption (WMD: 2.59, 95% CI: −6.61–1.42), or the duration of stimulation (WMD: −0.46, 95% CI: −1.64–0.71).
Conclusions: Before IVF treatment, obese and overweight women should lose weight by physical activity and/or dietary management because weight loss can improve pregnancy rate, reduce miscarriage rate, and meliorate live birth rate. At the same time, further prospective RCTs are required to establish which methods of weight loss are most suited to this purpose, as well as determining whether cut points for body mass index need to be recommended before accessing IVF.
Keywords: Dietary Management; In Vitro Fertilization; Obesity; Weight Loss
|How to cite this article:|
Song JY, Xiang S, Sun ZG. Effect of weight loss on In Vitro fertilization treatment outcome. Reprod Dev Med 2017;1:210-5
| Introduction|| |
Obesity has become a worldwide epidemic, with approximately 1.9 billion adults currently estimated to be overweight and 600 million estimated to be obese. The number of obese communities is also on the rise worldwide. Women of child-bearing age have not been spared from this dramatic trend, with 23% of this cohort now considered obese. Obesity is apt to result in a variety of health problems including adverse effects on reproductive health. Compared with women with normal body mass index (BMI) (≥18.5–24.9 kg/m2), the risk of infertility in women with elevated BMI (≥25 kg/m2) has tripled due to hypothalamic–pituitary–ovary axis disorders, menstrual changes, and ovulation abnormalities, as well as social and psychological factors., Furthermore, the incidence of pregnancy complications in obese women has also relatively increased; these complications include gestational diabetes, hypertension, premature birth, and cesarean section. Until recently, there has remained controversy over the impact of elevated BMI on the outcome of assisted reproductive technology (ART). Although some studies have reported that BMI has no adverse effect upon the results of in vitro fertilization (IVF),, others have associated increased BMI with notable detrimental effects. These included the need for higher doses of gonadotropins, higher cycle cancellation rates, fewer oocytes obtained, lower pregnancy, lower live birth rates, and lower abortion rates.,,, A recent systematic review concluded that elevated BMI had a negative impact on pregnancy rates, live birth rates, and spontaneous abortion rates after IVF treatment. Since the publication of this review, numerous studies have been released investigating the link between raised BMI and IVF outcomes. Considering the above mentioned, the aim of this study was to perform an up-to-date systematic review of existing literature to evaluate the impact of weight loss on the IVF treatment and, if possible, to determine the influence of different weight loss regimens on IVF outcome separately.
| Methods|| |
During this systematic review, we strictly adhered to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (http://www.prisma-statement.org) where possible. Since it considered only past data in extant studies and these data were managed in a way that excludes the possibility of subjects' identification, Institutional Review Board approval was not necessary for the present study.
“Obesity,” “obese,” “overweight,” “weight decrease,” “weight loss,” “weight change,” “weight reduce,” “physical activity,” “exercise,” “diet,” “bariatric surgery,” “in vitro fertilization,” “embryo transfer,” “intra-cytoplasmic sperm injection,” “assisted reproduction techniques,” “assisted reproductive technology,” “clinical trial,” “randomized clinical trial,” “randomized controlled trial,” and “RCT” were used as the keywords for the literature searches in the PubMed, Cochrane Library, ClinicalTrial.gov, Chinese Biomedical Database, and China National Knowledge Infrastructure databases. The retrieval time assessed was from the first publication of the journal to the end of August 2017. References included among the studies were also included in the study.
Inclusion and exclusion criteria
Studies were to be selected if the target population was obese women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment, and the interventions were weight loss including physical activity, dietary management, and bariatric surgery. Studies were identified through a two-stage process. First, two reviewers (S.X. and J.Y.S.) scanned the titles and abstracts from the electronic searches independently, and full manuscripts of all citations that explicitly or possibly accorded with the predefined selection criteria were obtained. Second, final inclusion or exclusion decisions were made on examination of the full manuscripts. Assessment of the manuscripts was performed, respectively, by two reviewers (S.X. and J.Y.S.), and any differences or contradictions with respect to inclusion were resolved by accordance after negotiation with a third reviewer (Z.G.S.).
Data extraction and quality assessment
The following data were recorded from each of the studies: demographic (author, type of study, country of origin, etc.), procedural (number of patients included, populations, type of protocol used for recipient preparation, etc.), and outcome data (clinical pregnancy rate, live birth rate, number of retrieved oocytes, etc.).
The quality assessment of RCTs was compiled using Cochrane's risk of bias tool. The information on the method of randomization, allocation concealment, blinding, intention-to-treat analysis, and follow-up rates was explored by retrieving the full-text literatures and by contacting the authors if detailed interpretation was needed.
The primary outcomes were the recipient clinical pregnancy and live birth rate per cycle attempt. Secondary outcome measures were the number of retrieved oocytes, duration of stimulation, total gonadotropin consumption, and the miscarriage rate per initial cycle.
All statistical analyses were performed using STATA software (version 12.0, Stata Corp., LLC, TX, USA). Binary data were expressed as risk ratios (RR s) with 95% confidence intervals (CI s). Continuous variables were expressed as weighted mean differences (WMDs) with 95% CI. Heterogeneity was evaluated using Chi-square tests and I2-index values, and the P value(s) were reported for each outcome. If significant heterogeneity was absent (I2<25% or >50% with P > 0.1), the meta-analysis used a fixed effects model. If not (I2 ≥50% or I2 >25% with P < 0.1), the meta-analysis used a random effects model.
| Results|| |
The preliminary literature search yielded 381 studies. Screening of the titles and abstracts resulted in 19 published articles that had possibly researched the effect of weight loss on IVF outcomes for obese and overweight women. There is an authoritative definition of which BMIs constitute being overweight (BMI ≥25–29.9 kg/m2) or obese (BMI ≥30 kg/m2). After reading the papers, only seven studies (924 patients) finally met our inclusion criteria.,,,,,, Although the cited studies used different methods for weight loss, they meet all inclusion criteria, so we included each of these studies in whole. The literature screening process and results are shown in [Figure 1], and the basic characteristics of the accepted papers are shown in [Table 1]. The quality assessment results are shown in [Table 2].
|Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart on study selection for systematic review.|
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Clinical pregnancy rate
Six of the seven studies reported patients' clinical pregnancy rate as an outcome. Pooling of results from those six studies showed markedly significant differences in clinical pregnancy rate per cycle attempt: RR: 1.61 (95% CI: 1.15–2.27; P = 0.006; heterogeneity P = 0.018; I2 = 63.4%, random effects model [Figure 2]). An influence analysis was carried out after ruling out any document in turn. No studies were found to have an impact on the outcome as a source of heterogeneity.
|Figure 2: Forest plot comparing the clinical pregnancy rate per woman randomized between the intervention group and control group.|
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Live birth rate
Meta-analysis of five studies that reported live birth rate as an outcome showed highly significant statistical differences between the intervention and control groups: RR: 1.86 (95% CI: 1.41–2.45; P < 0.001; heterogeneity P = 0.399; I2 = 1.2%, fixed effects model [Figure 3]).
|Figure 3: Forest plot comparing the live birth rate per woman randomized between the intervention group and control group.|
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The number of retrieved oocytes
A total of four studies were included in the meta-analysis of the number of retrieved oocytes. There was heterogeneity (P < 0.001, I2 = 94.1%) among the trials; therefore, the random effects model was used for the meta-analysis. The results indicated that there was no statistically significant difference in the number of retrieved oocytes between the two groups (WMD [95% CI] = 0.84 [−0.12, 1.79], P = 0.086 [Figure 4]).
|Figure 4: Forest plot comparing the number of retrieved oocytes per woman randomized between the intervention group and control group.|
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Duration of stimulation
A total of three studies were included in the meta-analysis of the number of retrieved oocytes. Significant heterogeneity (P < 0.001, I2 = 96.3%) was found among the trials; therefore, the random effects model was used for the meta-analysis. The results indicated that there was no statistically significant difference in the number of retrieved oocytes between the two groups (WMD [95% CI] = −0.46 [−1.64, 0.71], P = 0.44 [Figure 5]).
|Figure 5: Forest plot comparing the duration of stimulation per woman randomized between the intervention group and control group.|
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Total gonadotropin consumption
A total of three studies were included in the meta-analysis of the total gonadotropin consumption. Significant heterogeneity (P < 0.001, I2 = 99.4%) was found among the trials; therefore, the random effects model was used for the meta-analysis. The results indicated that there was no statistically significant difference in total gonadotropin consumption between the two groups (WMD [95% CI] = −2.59 [−6.61, 1.42], P = 0.206 [Figure 6]).
|Figure 6: Forest plot comparing the total gonadotropin consumption per woman randomized between the intervention group and control group.|
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A total of six studies were included in the miscarriage rate meta-analysis. There was no heterogeneity (P = 0.697, I2 = 0%) among the trials; therefore, the fixed effects model was used for the meta-analysis. The results indicated that there was a statistically significant difference in the miscarriage rate between the two groups (RR [95% CI] = 0.56 [0.34, 0.93], P = 0.026 [Figure 7]).
|Figure 7: Forest plot comparing the miscarriage rate per woman randomized between the intervention group and control group.|
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| Discussion|| |
Summary of main results
Results of our meta-analysis mainly focused on the effectiveness of weight loss before IVF. Concerning effectiveness, this review was underpowered to detect a difference in the number of oocytes retrieved, gonadotropin consumption, and duration of stimulation, but there was a trend toward benefit with the use of the weight loss intervention. This could be related to the smaller number of trials included.
However, regarding the main outcome measures of effectiveness, clinical pregnancy rate, miscarriage rate, and live birth rate all showed significant differences between the intervention and control groups. This indicates that weight loss before the IVF leads to a better reproductive outcome, even if no significant differences were found among secondary outcomes. Previous studies have suggested that obesity appears to affect the results of ART, providing more evidence that pathology exceeds the ovulatory barrier.,,, The oocyte, preimplantation embryo, and endometrial receptivity are affected by an obese environment. This may be the reason for the increase in pregnancy and live birth rate after weight loss.
According to our results, weight loss can effectively reduce the incidence of miscarriage rate without affecting the reproductive outcome. Therefore, weight loss should be used as widely as possible in patients who are overweight or obese.
Comparisons with other studies
A recent systematic review published in 2014 assessed the effect of weight loss on pregnancy outcomes in overweight and/or obese women using ARTs. This review included literature in which the methods of assisted pregnancy included not only IVF and ICSI but also routine ovulation induction and intrauterine insemination. It was not feasible to pool the data from these studies for meta-analytic purposes due to poor quality reporting, as well as wide differences in the methods of assisted reproduction and outcome measures, which included spontaneous conception. While the overall quality of the studies included in the previous review was poor, its conclusions support the clinical recommendation of advising overweight and/or obese women to lose weight before IVF.
Limitations of this study
Some clinical heterogeneity (i.e., methods of weight loss) existed among the trials, but owing to the limited number of studies identified, it was not viable to perform a subgroup analysis.
In conclusion, overall, the results support the clinical recommendation of encouraging overweight and/or obese women to lose weight before IVF. Prospective randomized controlled trials should establish efficacious evidence-based guidance for weight loss interventions in overweight and/or obese women before IVF treatment. At the same time, further prospective RCTs are required to establish which methods of weight loss are most suited to this purpose, as well as determining whether cut points for BMI need to be recommended before using IVF.
The authors are grateful to the authors of the studies from which data were provided for systematic review and meta-analysis.
This work was supported by the National Natural Science Fund project (No. 81373676, 81674018).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]