|Year : 2016 | Volume
| Issue : 2 | Page : 75-79
Role of obesity in female infertility and assisted reproductive technology (ART) outcomes
Munazzah Rafique1, Ayesha Nuzhat2
1 Head of Data Abstraction, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
2 Faculty of Medicine, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
|Date of Web Publication||13-Jan-2017|
Head of Data Abstraction, King Fahad Medical City, PO 59046, Riyadh - 11525
Kingdom of Saudi Arabia
Source of Support: None, Conflict of Interest: None
Introduction: Obesity is a preventable catastrophic pandemic in developed countries, and its occurrence is increasing in Saudi Arabia. One of the consequences of obesity is infertility, which is prevalent in 9–15% of the population.
Objective: To evaluate the impact of obesity on female infertility.
Materials and Methods: A retrospective study was performed in 196 infertile female patients of the reproductive age group seeking help in the reproductive unit of King Fahad Medical City, Riyadh. Data regarding age, duration of infertility, cause of infertility, body mass index (BMI), and their fertility outcomes were collected and evaluated using the Statistical Package for the Social Sciences version 20 (IBM Corp., NY).
Results: In this study, primary and secondary infertilities were not statistically associated with female BMI, although maximum number of patients was reported in the overweight and obese classification. Out of 65 patients in the overweight group, 28 (43.1%) patients with primary infertility and 37 (56.9%) with secondary infertility had BMI between 25 and 29.9; similarly, in the obese group, out of 94 patients, 46 (48.9%) patients with primary infertility and 48 (51.1%) with secondary infertility had BMI between 25 and 29.9. There was overall, statistically significant difference (P = 0.029) between response to assisted reproductive technology and female BMI. Out of the 65 overweight patients, 28 (43.1%) of them and, out of 94 obese patients, 25 (26.6%) of them were pregnant by in vitro fertilization; 29.2% of the overweight and 20.2% of the obese women had successful pregnancy.
Conclusion: The likelihood of successful pregnancy among obese women is less compared to normal weight women.
Keywords: Assisted reproductive technology (ART), infertility, obesity, polycystic ovaries (ultrasound diagnosis)
|How to cite this article:|
Rafique M, Nuzhat A. Role of obesity in female infertility and assisted reproductive technology (ART) outcomes. Saudi J Obesity 2016;4:75-9
| Introduction|| |
Obesity is globally escalating and leads to rise in associated morbidity and mortality. It is the fifth leading risk for global deaths. The prevalence of obesity in Kingdom of Saudi Arabia is 35.5%.
In women, though a critical mass of adipose tissue is needed for the proper development of the female reproductive function, obesity leads to menstrual disturbances and subfertility. The severity of obesity and the distribution of fat tissue dramatically impact the female reproductive system and fertility potential. Obesity is associated with various reproductive concerns including anovulation, infertility, increased risk of miscarriage, and poor neonatal and maternal pregnancy outcomes. Obesity in women with body mass index (BMI) > 30 kg/m2 led to ovulatory disorders, menstrual irregularities, hirsutism, virilization, and decreased contraceptive efficacy due to hormonal imbalances.,, The main factors associated with the implication may be insulin excess and insulin resistance. The proposed mechanisms are alterations in the hypothalamic–pituitary–ovarian axis, oocyte quality, and endometrial receptivity. The risk of ovulatory infertility is highest in obese women. Basal luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels are lower in obese women with the decrease in ovarian reserve when compared to normal weight women.
Infertility is characterized as having a waiting time of more than 12 months to achieve pregnancy that resulted in a live birth. Although the global prevalence of infertility is difficult to determine, it affects one in four couples of developing countries. According to Boivin, infertility prevalence is approximately 9–15%, and it is increasing. All types of assisted reproduction methods are affected by obesity including the use of gonadotropins in ovulation induction and in vitro fertilization (IVF). The objective of this study was to evaluate the impact of obesity on female infertility.
| Materials and Methods|| |
The study received ethics approval from the institutional ethics committee responsible for human research in King Fahad Medical City, Riyadh, Saudi Arabia (Institutional Review Board (IRB) number: 15-125).
Infertile women who came for infertility workup in the Reproductive Endocrinology and Infertility Medicine Department (REIMD) of King Fahad Medical City, Riyadh, Saudi Arabia were included in the study. World Health Organization (WHO) criteria were used to classify women into underweight (BMI: <18.50 kg/m2), normal weight (BMI: 18.50–24.99 kg/m2), overweight (BMI: 25.00–29.99 kg/m2), or obese (BMI: >30.00 kg/m2). According to WHO, 2015 fact sheet, infertility is defined as waiting time of more than 12 months to achieve a pregnancy that resulted in a live birth. Our sample comprised of women aged 17–40 years, infertile, and Saudi nationals. The study excluded women with any medical or genetic illness predisposing to obesity. From June 2012 to February 2013, random sampling technique was used to select 127 infertile women out of a total population of 196 infertile patients, who were visiting REIMD for treatment.
The variables including BMI, menstrual irregularities, ultrasonography finding, basal hormonal status, infertility duration, assisted reproductive technology (ART) cycle parameters, and outcome were recorded. From each patient, 5 ml of blood was obtained, labeled with a hospital registration number, sent to the lab for investigation, and the cut-off value set. Hormonal status was evaluated by measuring serum T3, T4, and thyroid-stimulating hormone (TSH) by immunoassay method. As per kit supplier’s instruction, normal T3, T4, and TSH levels were 0.8–1.90 ng/ml, 5–13 μg/dl, and 0.4–5.5 μIU/ml, respectively, wherein serum FSH (5–20 IU/ml), LH (5–20 IU/ml), and serum prolactin (102–496 mIU/L) were the normal lab reference values.
ART includes a range of methods used to circumvent human infertility, including IVF, embryo transfer, gamete intrafallopian transfer, and artificial insemination.
In our study, the following outcomes were recorded:
- Successful pregnancy;
- No pregnancy;
- Ectopic pregnancy;
- Unknown (loss of follow-up).
Data were entered and analyzed through the Statistical Package for the Social Sciences version 22 (IBM Corp., NY).
All categorical variables like gender fertility, types of infertility, and duration of fertility were presented as numbers and percentages, whereas continuous variables like age and BMI were expressed as mean ± standard deviation (SD). Chi-square/Fisher’s exact test was used to determine the significant relationship between categorical variables. Independent sample t-test was used to determine the significant mean difference between female factor and lab investigations with other parameters. P-value of less than 0.05 was considered as statistically significant.
| Results|| |
As shown in [Table 1], among 127 selected cases of female infertility out of 196, 33.2% were overweight and 48% were obese. There were 29.6% women who had menstrual irregularities, and 70.4% did not have any menstrual disturbance. Physical examination was unremarkable in majority of the women (83.7%). Ultrasound finding of polycystic ovaries (PCO) was reported in 28.1% of the women. There were 65 (33.2%) women who got pregnant by ART, with successful pregnancy resulting in 24% of the obese [Table 1].
Mean and SD of all measurements and results of the lab investigations in these women are revealed in [Table 2]. In infertile women, there was decrease in the level of FSH, LH, and estradiol but increase in the level of serum testosterone.
In [Table 3], the maximum duration of infertility among overweight (41.5%) and obese women (35.1%) is 3–4 years. Though underweight women have primary infertility (66.7%), 56.9% of overweight and 51.1% of obese women have secondary infertility with a P-value of 0.009. In 70.8% of overweight and 66% of obese women, the menstrual cycle was regular. Most common ultrasound manifestation in overweight (30.8%) and obese (28.7%) women was PCO. Women having >30 BMI or obese patients were considered as high risk for the unsuccessful cycle. With IVF, 29.2% of overweight and 20.2% of obese women had successful pregnancy.
|Table 3: Association between BMI and infertility and lab investigation parameters|
Click here to view
| Discussion|| |
The spectrum of reproductive problems associated with obesity encompasses a broad range of disorders. The consequences of obesity on the female reproductive system are diverse including menstrual disorders, infertility, miscarriage, poor pregnancy outcome, impaired fetal well being, and diabetes mellitus.,
Our study revealed that women with BMI > 25 are at risk of infertility. The outcome of successful pregnancy was less in obese women. Ramlau-Hansen et al., in their Danish study, concluded that the time to pregnancy increases with increase in BMI and is associated with subfecundity. According to our study, the maximum duration of infertility among overweight (41.5%) and obese women (35.1%) was 3–4 years. Hartz et al. established, by his study of 26,638 women to show the association of obesity with infertility and menstrual abnormalities, that 12,000 women were reported to have irregular menstruation and hirsutism. There were 29.2% of overweight and 34% of obese women having irregular cycle, and our study did not determine hirsutism relationship.
Conferring to Talmor and Dunphy, ovulatory defects and unexplained causes account for >50% of infertile etiologies with a significant proportion of these cases either directly or indirectly related to obesity. Our study also produces results with 1% of female etiology referring to anovulation and 23.5% women having unexplained cause for their infertility. Pergola et al. in his study determined the effect of obesity on gonadotropin, estradiol, and inhibin B levels in infertile women and established significant relation statistically to lower FSH, LH, inhibin B, and estradiol levels in the early follicular phase of overweight and obese infertile women. Pergola et al. anticipated it to be due to direct inhibitory effect of BMI on gonadotropin and estradiol production. Our study also reflected a decrease in follicular phase levels of FSH (mean = 6.8 IU/L), LH (mean = 8.1 IU/L), and serum estrogen (mean 350 pmol/L), as well as high serum testosterone level 2.04 nmol/L (range 0.02–0.34 nmol/L) in obese women with BMI > 30. Caillon et al. conducted a study to see outcomes of high BMI women to ART outcomes on 582 women undergoing ART treatment in France. The study determined that spontaneous fertility as well as ART cycles results are impaired in obese women. In obese women, higher doses of gonadotropins are required to obtain equivalent ovarian response, however, even then, ART cycles trend toward increasing transfer cancellation and miscarriage rates leading to poorer ART outcome. Our results show consistent results with only 29.2% of overweight and 20.2% of obese women having a successful pregnancy.
Thus, cumulating infertility and obesity poses challenges in short- and long-term management of these patients because of synergistic adverse effects., Weight loss assists in improving the menstrual cycle and promoting spontaneous ovulation and fertility by changes in sensitivity to insulin. Losing weight can ameliorate many of these problems, and there is a need for appropriate counseling and preventive intervention. Further work is required to clarify the underlying pathophysiology responsible for adverse effects of obesity on reproduction so that novel treatment approaches may be developed.
It is single infertility center study that is conducted on a cohort of women coming for infertility treatment. Later, this study can be expanded at regional and national levels.
| Conclusion|| |
Accordingly, the women who are overweight and obese are at increased risk of infertility as shown by statistically significant association with all parameters. Even if these women are provided with ART facilities, their outcome is not very optimistic. Application of obesity prevention program in infertility clinics can develop spontaneous pregnancies as well as improve the outcomes of artificial fertilization techniques.
Because our study highlighted the association of female BMI to infertility, we recommend to conduct a study on the association of male obesity with infertility and also to explore the impact of couple obesity on infertility.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Talmor A, Dunphy B. Female obesity and infertility. Best Pract Res Clin Obstet Gynaecol 2015;29:498-506.
World Health Organization. Obesity: Preventing and Managing the Global Epidemic. WHO Obesity Technical Report Series 2000, No. 894. Geneva, Switzerland: World Health Organization; 2000.
Al-Nozha MM, Al-Mazrou YY, Al-Maatouq MA, Arafah MR, Khalil MZ, Khan NB et al.
Obesity in Saudi Arabia. Saudi Med J 2005;26:824-9.
Lake JK, Power C, Cole TJ. Women’s reproductive health: The role of body mass index in early and adult life. Int J Obes Relat Metab Disord 1997;21:432-8.
Diamanti-Kandarakis E, Bergiele A. The influence of obesity on hyperandrogenism and infertility in the female. Obes Rev 2001;2:231-8.
Linné Y. Effects of obesity on women’s reproduction and complications during pregnancy. Obes Rev 2004;5:137-43.
Pasquali R, Patton L, Gambineri A. Obesity and infertility. Curr Opin Endocrinol Diabetes Obes 2007;14:482-7.
Klenov VE, Jungheim ES. Obesity and reproductive function: A review of the evidence. Curr Opin Obstet Gynecol 2014;26:455-60.
Grodstein F, Goldman MB, Cramer DW. Body mass index and ovulatory infertility. Epidemiology 1994;5:247-50.
Caillon H, Fréour T, Bach-Ngohou K, Colombel A, Denis MG, Barrière P et al.
Effects of female increased body mass index on in vitro
fertilization cycles outcome. Obes Res Clin Pract 2015;9:382-8.
Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: Potential need and demand for infertility medical care. Hum Reprod 2007;22:1506-12.
Norman RJ, Clark AM. Obesity and reproductive disorders: A review. Reprod Fertil Dev 1998;10:55-63.
Metwally M, Li TC, Ledger WL. The impact of obesity on female reproductive function. Obes Rev 2007;8:515-23.
Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sørensen TI, Olsen J. Subfecundity in overweight and obese couples. Hum Reprod 2007;22:1634-7.
Hartz AJ, Barboriak PN, Wong A, Katayama KP, Rimm AA. The association of obesity with infertility and related menstrual abnormalities in women. Int J Obes 1978;3:57-73.
De Pergola G, Maldera S, Tartagni M, Pannacciulli N, Loverro G, Giorgino R. Inhibitory effect of obesity on gonadotropin, estradiol, and inhibin B levels in fertile women. Obesity 2006;14:1954-60.
Zaadstra BM, Seidell JC, Van Noord P, te Velde ER, Habbema JD, Vrieswijk B et al.
Fat and female fecundity: Prospective study of effect of body fat distribution on conception rates. BMJ 1993;306:484-7.
[Table 1], [Table 2], [Table 3]