Abstract
Obesity is detrimental to general health and also reproductive health. This study aimed to evaluate whether weight reduction in obese infertile women prior to in vitro fertilization reduces the total gonadotropin dose and improves pregnancy outcomes. This retrospective cohort study was performed at the Jiaxing Maternity and Child Health Care Hospital between January 2017 and January 2022, and 197 women were enrolled. The women were divided into 2 groups according to the weight loss goal of 5%: weight reduction group A (≥weight loss goal of 5%) and control group A (<weight loss goal of 5%). According to the weight loss goal of 10%, we also divided the weight reduction B group (≥10% weight loss goal) and the control B group (<weight loss goal). Compared to the control A group, the weight reduction A group had a significantly lower total gonadotropin dose (P = .001); however, there was no significant difference in clinical pregnancy and live birth rates. The weight reduction B group had a significantly higher clinical pregnancy rate than the control B group (P = .002), as well as a significantly higher live birth rate (P = .004). Weight loss (≥5%) lasting 3 to 6 months did not improve the clinical pregnancy and live birth rates. However, weight loss (≥5%) can decrease the total gonadotropin dose in obese women scheduled for in vitro fertilization. Weight loss of up to 10% can significantly decrease the total gonadotropin dose, improve the clinical pregnancy rate, and increase the live birth rate.
Keywords: body mass index, clinical pregnancy rate, in vitro fertilization, obese, weight loss
1. Introduction
The prevalence of obesity worldwide has increased over the past 3 decades.[1] Obesity represents a sharply increasing threat to the health of populations in both developed and developing countries, especially women of reproductive age.[2] Most studies clearly demonstrate that obesity negatively impacts fertility in women with ovulatory disorders.[3–5] However, during regular menstrual cycles, the fecundity of obese women remains reduced.[6] Obese women have 2-fold greater odds of pregnancy loss than normal-weight women.[7] Obese women also have adverse pregnancy outcomes with assisted reproductive technology, including a lower clinical pregnancy rate, lower live birth rate, and higher miscarriage rate.[8] Weight loss can improve spontaneous ovulation and increase the spontaneous pregnancy rate.[9] However, some studies showed that there was no significant difference in gonadotropin dose, clinical pregnancy rate, or miscarriage rate in infertile obese women with weight loss prior to in vitro fertilization (IVF).[10]
The aim of this study was to evaluate the effect of weight loss in infertile obese women before IVF on the total gonadotropin dose, as well as pregnancy outcomes such as clinical pregnancy and live birth rates.
2. Materials and methods
2.1. Ethics statement
This study was approved by the ethics committee of Jiaxing University-affiliated Maternity and Child Hospital (approval number:2017-07). All women had written informed consent.
2.2. Study design and participants
This retrospective cohort study was performed between January 2017 and January 2022 at the Fertility Unit of the Hospital Jiaxing Maternity and Child Health Care Hospital, Zhejiang, China. All the studies were conducted in accordance with the Declaration of Helsinki (1964). Inclusion criteria for eligible patients were as follows: body mass index (BMI ≥ 30 kg/m2); age 18 to 38 years; first IVF/intracytoplasmic sperm injection (ICSI) cycle; short-acting gonadotropin-releasing hormone (GnRH) agonist long protocol; women were excluded from the trial if they had diminished ovarian reserve (defined as an antral follicle count of ≤5 or baseline follicle-stimulating hormone levels ≥ 10 IU/L), irregular uterine bleeding, oocyte donation, pre-implantation genetic diagnosis, and Cushing syndrome.
We advised obese women to participate in a weight management program for 3 to 6 months before undergoing their first IVF/ICSI cycle. Women were divided into 2 groups according to the weight loss goal of 5%: weight reduction group A (≥weight loss goal of 5%) and control group A (<weight loss goal of 5%). According to the weight loss goal of 10%, we also divided another 2 groups: weight reduction B group (≥weight loss goal of 10%) and control B group (<weight loss goal of 10% or no weight loss).
2.3. IVF procedure
Controlled ovarian hyper-stimulation was performed using a short-acting GnRH agonist long protocol. Recombinant follicle-stimulating hormone (Merck Serono) was started at least 14 days after the downregulation of GnRH agonist for complete suppression of estradiol from 75 to 300IU/d. Ovulation was induced with human chorionic gonadotropin, and approximately 36 hours later, oocyte retrieval was performed under transvaginal ultrasonographic guidance. Fertilization was carried out using the standard IVF technique; if male infertility or fertilization failure occurred, oocytes were inseminated by ICSI. Embryo transfer was mostly performed using cleaving stage embryos (day 3). If a patient was at risk of ovarian hyperstimulation syndrome, the embryo was vitrified and transferred to a subsequent substituted cycle.
2.4. Statistical analysis
Data were analyzed using SPSS version 18.0 (SPSS Inc., Chicago, IL) software. Variables are presented as the mean ± standard deviation. The significance of differences between groups was determined using an unpaired t-test for independent variables, repeated measures, or the Mann–Whitney U test (for non-normally distributed data). Normal distribution was assessed using the Kolmogorov–Smirnov test. Differences in frequencies were tested using the chi-squared test. Statistical significance was set at P < .05.
3. Results
3.1. Baseline characteristics and outcome of IVF cycle in A group
A total of 98 women were included in the weight reduction group A, and 99 women were included in the control group. The baseline characteristics did not show statistically significant differences in age, infertility factors, and serum estradiol levels on the day of the last ultrasound. There was a significant difference in the original BMI (before weight management) (P = .001). After weight loss, the BMI of the weight reduction A group was significantly lower than that of the control A group (P = .001). There was a significant difference in the total gonadotrophin dose between the weight reduction and control groups (P = .001). There were no significant differences in the day of gonadotropin stimulation, number of total oocytes retrieved, fertilization rate, high-quality embryos, clinical pregnancy, biochemical pregnancy, miscarriage rate, live birth rate, or twin birth rate (Table 1).
Table 1.
Baseline characteristics and outcome of IVF cycle in the weight reduction A group and control A group.
| Weight reduction A group (98) | Control A group (99) | P | |
|---|---|---|---|
| Age (yr) | 29.34 ± 3.87 | 29.87 ± 4.46 | .533 |
| Body mass index (kg/m2) | 32.28 ± 2.18 | 30.96 ± 1.24 | .001 |
| Body mass index (weight loss) (kg/m2) | 28.56 ± 1.94 | 30.79 ± 1.09 | .001 |
| Infertility factor Tubal Ovulatory Male Endometriosis Unexplained Other |
33 (33.67%) 48 (48.98%) 8 (8.16%) 3 (3.06%) 4 (4.08%) 2 (2.05%) |
47 (47.47%) 35 (35.35%) 11 (11.11%) 2 (2.02%) 3 (3.03%) 1 (1.01%) |
.087 |
| Oestradiol on last ultrasound (pmol/L) | 10,335.50 ± 6850.08 | 10,226.87 ± 5920.41 | .905 |
| Total gonadotrophin dose (IU) |
2907.01 ± 1063.90 | 3413.13 ± 1080.97 | .001 |
| Day of gonadotrophin stimulation (d) | 12.47 ± 2.22 | 13.05 ± 2.28 | .071 |
| No. of oocytes retrieval | 14.83 ± 7.82 | 13.66 ± 6.81 | .268 |
| Rate of fertilization (%) | 0.70 ± 0.23 | 0.68 ± 0.23 | .558 |
| Rate of normal fertilization (%) | 0.64 ± 0.22 | 0.60 ± 0.23 | .214 |
| No. of good-quality embryos Day 3 | 4.96 ± 4.06 | 4.20 ± 3.87 | .181 |
| Clinical pregnancy rate (%) | 54/98 (55.10%) | 45/99 (45.45%) | .199 |
| Biochemical pregnancy rate (%) | 6/60 (10%) | 6/51 (13.04%) | .765 |
| Miscarriage rate (%) | 6/54 (11.11%) | 6/45 (13.33%) | .736 |
| Live birth rate (%) | 48/98 (48.98%) | 39/99 (39.39%) | .176 |
| Twin birth rate (%) | 9/48 (18.75%) | 8/39 (20.51%) | .837 |
IVF = in vitro fertilization.
3.2. Baseline characteristics and outcome of IVF cycle in B group
A total of 56 women were included in weight reduction group B and 141 women were included in the control B group. The baseline characteristics did not show statistically significant differences in age, infertility factors, and serum estradiol levels on the day of the last ultrasound. There was a significant difference in the original BMI (before weight management) (P < .001). After weight loss, the weight reduction in group A was significantly lower than that in group A (P < .001). There was a significant difference in the total gonadotrophin dose between the weight reduction and control groups (P = .004). The weight reduction group had a significantly higher clinical pregnancy rate and live birth rate than the control B group (P = .002 and P = .004, respectively). There were no significant differences in biochemical pregnancy, miscarriage, and twin birth rates (Table 2).
Table 2.
Baseline characteristics and outcome of IVF cycle in the weight reduction B group and control B group.
| Weight reduction B (≥10%) (56) | Control B group (141) | P | |
|---|---|---|---|
| Age (yr) | 28.87 ± 3.68 | 29.90 ± 4.33 | .120 |
| Body mass index (kg/m2) | 32.97 ± 2.45 | 31.08 ± 1.27 | <.001 |
| Body mass index (weight loss) (kg/m2) | 27.79 ± 2.34 | 30.55 ± 1.59 | <.001 |
| Infertility factor Tubal Ovulatory Male Endometriosis Unexplained Other |
18 (32.14%) 27 (48.22%) 5 (8.93%) 2 (3.57%) 2 (3.57%) 2 (3.57%) |
51 (36.17%) 61 (43.27%) 13 (9.22%) 7 (4.96%) 6 (4.25%) 3 (2.13%) |
.816 |
| Oestradiol on last ultrasound (pmol/L) | 10,366.03 ± 6401.01 | 10,247.10 ± 6399.28 | .906 |
| Total gonadotrophin Dose (IU) |
2790.27 ± 812.40 | 3273.32 ± 1115.50 | .004 |
| Day of gonadotrophin stimulation (d) | 12.46 ± 2.02 | 12.88 ± 2.35 | .246 |
| No. of oocytes retrieval | 15.07 ± 7.94 | 13.91 ± 7.08 | .320 |
| Rate of fertilization (%) | 0.73 ± 0.23 | 0.67 ± 0.22 | .074 |
| Rate of normal fertilization (%) | 0.66 ± 0.23 | 0.60 ± 0.22 | .079 |
| No. of good-quality embryos Day 3 | 4.48 ± 2.96 | 4.62 ± 4.31 | .830 |
| Clinical pregnancy (%) | 36/56 (64.28%) | 56/141 (39.72%) | .002 |
| Biochemical pregnancy (%) | 4/40 (10%) | 7/63 (11.11%) | .859 |
| Miscarriage rate (%) | 4/36 (11.11%) | 7/56 (12.5%) | .841 |
| Live birth rate (%) | 32/56 (57.14%) | 49/141 (34.75%) | .004 |
| Twin birth (%) | 7/32 (21.87%) | 10/49 (20.41%) | .874 |
IVF = in vitro fertilization.
4. Discussion
This retrospective analysis study showed that weight loss (≥5%) lasting 3 to 6 months, can significantly decrease the total gonadotrophin dose in obese women scheduled for IVF. Balen et al showed that a higher threshold dose of gonadotropins was increased in parallel with a BMI.[11] A similar investigation suggested that BMI is a significant predictor of gonadotrophin doses for ovulation induction.[12] A higher BMI may lower the bioavailability of gonadotrophins irrespective of the administration route.[13] Our study demonstrated a significant decrease in the total gonadotrophin dosage after weight loss (≥5%).
This study demonstrated that weight loss > 5% could not improve pregnancy and live birth rates among obese patients with IVF. Nevertheless, when the weight loss was up to 10%, the clinical pregnancy and live birth rates achieved meaningful improvement. A randomized clinical trial[14] showed a loss of only 6.9% of initial body weight was sufficient to enhance the pregnancy rate. Nevertheless, other multicenter randomized clinical trials have shown that lifestyle interventions to decrease weight treatment did not result in a better live birth rate.[15] Clark et al[16] suggested that a weight loss of just 5 to 10% had progressively positive effects on reproductive outcomes. A retrospective cohort study showed that meaningful weight loss (≥10%) improved the conception and live birth rates in infertile obese patients.[17] Lu et al encouraged obese women to lose weight by up to a 10 to 15% reduction, not reaching normal BMI categories, which was useful in reducing the risks of some perinatal complications.[18] A 10% weight loss may be a more effective intervention that can achieve higher pregnancy and live birth rates.
A systematic review and meta-analysis noted that oocyte quality may be an overriding factor influencing IVF outcomes in obese women.[19] A 12-year retrospective cohort analysis showed that female obesity lowered reproductive outcomes, probably because of reduced uterine receptivity.[20] The maternal metabolic environment in obesity adversely affects oocyte quality and subsequent fertilization, including delayed embryonic development.[21] Based on our data, we found no significant differences in gonadotrophin stimulation, number of oocytes retrieved, fertilization rates, high-quality embryos obtained, and serum estradiol on the last ultrasound. Very few studies have investigated the significant effects of weight loss on the number of oocytes retrieved, fertilization rates, and high-quality embryos. The effects of BMI on oocyte and embryo development require further investigation.
There were some limitations to this study. First, this study was limited by its design as a retrospective cohort study. In addition, this study was a single-center study. As obese Chinese women of reproductive age were comparably little, the sample size was small. Larger studies are needed to explore this finding. Furthermore, we did not have data on the cumulative live birth rate. At last, the pattern of weight loss including regular physical activity, diet, and bariatric surgery was not specified.
5. Conclusion
In summary, weight loss (≥5%) lasting 3 to 6 months did not improve clinical pregnancy and live birth rates. However, weight loss (≥5%) can decrease the total gonadotrophin dose in obese women scheduled for IVF. Weight loss reaching 10% can significantly decrease the total gonadotropin dose, improve clinical pregnancy rates, and increase the live birth rate. We suggest that obese women scheduled for IVF perform meaningful weight loss (≥10%) prior to pregnancy, but do not reach the ideal BMI range.
Author contributions
Data curation: Weiping Fu, Chunxia Fang, Huan Zhou.
Formal analysis: Weiping Fu, Chunxia Fang.
Investigation: Weiping Fu.
Methodology: Chunxia Fang.
Project administration: Chunxia Fang.
Resources: Chunxia Fang.
Writing – original draft: Huan Zhou.
Writing – review & editing: Chunjuan Shen, Liping Wang.
Abbreviations:
- BMI
- body mass index
- GnRH
- gonadotropin-releasing hormone
- ICSI
- intracytoplasmic sperm injection
- IVF
- in vitro fertilization
This work was supported by the Science and Technology Bureau of Jiaxing City (grant number 2020AD30033).
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Shen C, Fu W, Fang C, Zhou H, Wang L. The impact of weight loss for obese infertile women prior to in vitro fertilization: A retrospective cohort study. Medicine 2023;102:10(e33009).
Contributor Information
Chunjuan Shen, Email: [email protected].
Weiping Fu, Email: [email protected].
Chunxia Fang, Email: [email protected].
Huan Zhou, Email: [email protected].
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