Effect of Weight Loss After Laparoscopic Sleeve Gastrectomy on Infertility of Women in Shiraz

Introduction

The link between obesity and polycystic ovarian syndrome (PCOS) is well-known. PCOS is usually associated with menstrual irregularities and hirsutism. PCOS affects between 12% and 21% of women of reproductive age, and the majority of these women remain undiagnosed. ¹ In ∼35% of patients with PCOS, it has been noted that obesity has detrimental effects on ovulation. Obesity has also been linked to poor obstetric outcomes, including congenital defects; miscarriages and preterm labor; perinatal morbidity and mortality; and pregnancy complications such as hypertension, gestational diabetes, thromboembolic disease, chorioamnionitis, and wound infection. Moreover, a direct correlation has been demonstrated between a higher body mass index (BMI) and infertility. ² The benefits of laparoscopy could be even more pronounced in patients with metabolic and hormonal complications. Several studies have been conducted to investigate the long-term implications of increased body mass on future fertility outcomes. ¹

In recent years, developments in bariatric surgery have become more progressive, such as laparoscopic sleeve gastrectomy (LSG), which is performed in severely overweight patients. ³ Obesity is linked to conditions such as type 2 diabetes, hypercholesterolemia, cardiopulmonary complications, hormonal disturbances, and even infertility. Obesity is associated with various reproductive sequelae, including anovulation, infertility, increased risk of miscarriage, and poor neonatal outcomes. The mechanism of how obesity affects female reproductive function is known. ¹ This mechanism is mediated by interaction between the hypothalamic–pituitary–ovarian axis, oocyte quality, and endometrial receptivity. Obesity is associated with decreased levels of sex-hormone–binding globulin, increased peripheral aromatization to estrogens, increased levels of free estradiol and testosterone, and increased insulin levels. Hyperinsulinemia causes hyperandrogenemia by increasing bioavailability of androgens and stimulating the ovaries to secrete androgen. It is known that obesity is associated in varying degrees with insulin resistance, dyslipidemia, hypertension, and varying components of metabolic syndrome. ⁴

However, data on the outcomes of LSG in obese patients with infertility are few. This study was designed specifically to compare the outcomes of LSG in obese patients with infertility before and after the surgery. Also, the impact of obesity on the outcome of infertility associated with PCOS was determined.

Materials and Methods

This was a retrospective analysis of data of 221 female patients who underwent LSG at Shahid Faghihi and Madar-va-Kodak Hospitals, in Shiraz, Iran. All patients were evaluated from digestive, nutritional, metabolic, cardiovascular, and mental perspectives. The patients were evaluated for bariatric surgery by a multidisciplinary committee including a psychologist, a nutritionist, surgeons, and sport physicians. Demographics, time from surgery, infertility (inability to achieve a conception for >12 months of cohabitation), and some complications were evaluated. Obesity and hyperandrogenism mainly presented by at least one or more of these problems such as polycystic ovaries (PCO), acne, hirsutism, and oligo/amenorrhea.

Each patient was evaluated carefully and the case was discussed in a multidisciplinary meeting. Inclusion criteria were defined as having medically indicated LSG (BMI: 25–65) and having provided written informed consent. Exclusion criteria for this study were: age <18 years or >65 years, BMI ≥65 kg/m², and history of substance abuse. Other exclusions were medical problems having negative effects on pregnancy outcomes (chronic hypertension, diabetes mellitus and chronic renal disorder, ovariectomy, tubectomy, adenectomy, thyroid derangements, hyperprolactinemia, congenital adrenal hyperplasia, androgen-secreting tumors and Cushing's syndrome). All women who became pregnant after surgery were given appointments and followed-up.

The study was approved by the ethics committee of the Shiraz University of Medical Sciences, in Shiraz, Iran. Statistical analysis was performed with SPSS 11.0 and by using mean values and comparison of data by a Student's t-test and a nonparametric Mann–Whitney U-test, with p = 0.05 as the significant value.

Results

Among the study patients, 52 were single and 169 were married; 23 married patients were in menopause. The patients had a mean age of 36.66 ± 0.7 (ranging from 18 to 63) years. The mean BMI before surgery was 43.99 ± 0.5 (ranging from 25.00 to 65.00 kg/m²; Table 1). Of 146 women who were of childbearing age, 21 (14.4%) were diagnosed as having PCO, based on clinical evaluations that 55 patients had irregular menstruation and, after surgery, 35 still had menstrual irregularity. A total of 15 patients who underwent LSG were infertile because of obesity, and 5 (33.33%) had infertility after 1 pregnancy. Seven infertile patients after surgery became fertile, and 40% of infertile patients had abortion at least one time (20% before surgery and 20% after surgery). The patients were evaluated at an average of 20 months after surgery.

Evaluation of educational status revealed that half of the women (47.7%) had up to high-school education, 36% had 4 years of university-level education, 54.2% had no occupation, and 29.5% were employed. Twenty percent of infertile women had 4 years of university-level education, other patients were less-educated, and 20% of them had an occupation. There were no significant differences in the incidence of infertility according to educational status or occupation. Although housewives comprised only ∼54.2% of the study population, their contribution to mean BMI was not significantly different from other patients. Eighty percent of infertile women used human chorionic gonadotropin, and 20% of them had intravenous gamete intrafallopian tube transfer treatment before surgery but did not become pregnant.

Of the infertile women, 60% had irregular menstruation and 50% had hirsutism before surgery; after surgery, 40% became regular in their menstruation and 10% had their hirsutism cured.

Diabetes resolved in 2 patients and improved in 1 patient by the end of 6 months, and hypertension resolved in 4 and improved in 3 patients. Diabetes mellitus in pregnancy was seen in 1 patient and hypertension in pregnancy was seen in 4 patients. The overall pregnancy rate was 46.67%, and the live birth rate was 33.34%, and 1 of these patients had hypertension during her pregnancy. Abortion and stillbirth rates were significantly increased in obese and grossly obese women, compared with patients who had normal BMIs. There is, however, need for caution in the interpretation of these results because of the small number of neonates involved.

Discussion

LSG is an effective procedure to reduce weight in obese patients and it improves many comorbidities.^5–9 In the current series, the mean % of excess weight loss after 6 months was 62.89%, and infertile women had a mean % of excess weight loss of 70.29% (Table 2). Lakdawala et al. ¹⁰ and Rosenthal et al. ¹¹ have reported a mean % of excess weight loss of 50.8% and 52.8% at the end of 6 months, respectively. Baltasar et al. reported a mean % of excess weight loss of 56.1% from 4 to 27 months after surgery. ¹²

Obesity is usually associated with an increased risk of miscarriage, hypertension, preeclampsia, and gestational diabetes. ¹ In the current study, 25 patients had abnormal deliveries before surgery, 15 patients were infertile, and 2 had abortions after surgery and 7 patients became pregnant, showing that they became fertile.

The main concerns after surgery are a relative malabsorptive state. The interval between surgery and pregnancy needs to be mentioned. Following LSG, there is a rapid weight loss that typically continues for 12–18 months and, therefore, pregnancy is not recommended for at least 1 year after surgery. The optimal interval between surgery and pregnancy is controversial, but it is necessary to have this interval, because, there is an increase in nutritional demands during pregnancy and this malabsorptive state may increase the risk of low birth weight, neonatal hypocalcemia, neural-tube defects, and intrauterine growth restriction. ¹³ Therefore, the importance of nutritional balance rather than the interval between surgeries to conception is the most important determinant.

This study demonstrated that PCO and irregular menstruation are commonly associated with infertility. In some investigations, frequency of obesity in women with polycystic ovaries and anovulation has been reported to be from 35% to 60%. ¹⁴ In the current study, the frequency of PCO was 15.7%, and 32% of these women were infertile. Tsur et al. and Musella et al. claimed that the menstrual pattern is dependent on the BMI and showed that weight reduction improves menstrual pattern, ovulation, and fertility.^4,14

The main findings of the current study are the effects of LSG on fertility outcome. The effect of weight loss at least >5% of the initial weight in these women was related to reduced insulin and free testosterone concentration that could have led to resumption of ovulation and pregnancy. ¹⁴ A BMI of <27 was reported to be sufficient for achieving improved menstrual function and ultimately pregnancy. ¹⁴ In one study, infertile obese women (BMI: 35.0–39.9) had a lifestyle intervention program and lost an average 10% of their weight, and achieved a pregnancy rate of 77% and a live birth rate of 67%. ¹⁵

In contrast, a Canadian study investigated the effects of BMI on hormonal requirements for ovarian stimulation and no significant difference occurred in pregnancy and live birth rates between various BMI groups. ¹ In a study by Kort et al., infertile patients with a BMI of 33 who had 10% weight loss achieved pregnancy (88%), compared with (54%) those patients who reduced their BMIs. ¹⁶ Based on the results of the current study, it seems that time and amount of weight loss is very important for fertility of patients.

Conclusions

In the current study population, the authors believe that LSG was an effective procedure to achieve weight loss in the short term in patients who were morbidly obese. This surgery can improve ovulatory cycles and conception rates in obese women. Pregnant women after undergoing LSG are still at high risk for abortion or preterm births. The decision to achieve pregnancy should be carefully considered, as should the effects of weight loss after this surgery on the reproductive potential; a time interval between surgery and pregnancy is mandatory in order to prevent nutritional deficiencies and abnormal fetal growth.