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Obesity and IVF

The United States has 97 million overweight or obese adults. Their risk of morbidity from hypertension, type 2 diabetes, coronary artery disease, stroke, gall bladder disease, sleep apnea, endometrial, breast, and colon cancer is increased. It is the second leading cause of preventable death in the US (1). Obesity is defined as a BMI>30 kg/m2. Normal weight is defined as BMI between 18.5 kg/m2 and 24.9 kg/m2. Overweight is defined as 25.0 kg/m2-29.9 kg/m2 and extreme obesity is >40 kg/m2. Many obese individuals of reproductive age attempt to conceive using ART. PCOS is a common indication for ART and in addition to hyperandrogenism and anovulation, approximately 70% are obese (mostly central obesity with an increased waist:hip ratio). Insulin resistance plays a role in the pathophysiology of the syndrome and may play a role in the eventual outcome with ART.

Lashen et al (2) examined the effects of BMI (Obese>27.9) on IVF. They examined amount and duration of gonadotropins, number of follicles aspirated, egg number, number of embryos, peak estradiol, clinical pregnancy rate, miscarriage rate, implantation rate, and incidence of OHSS compared to controls with normal BMI. The only difference was a lower peak estradiol level. Insulin levels were not assessed in this study. Fedorcsak et al (3) assessed the impact of obesity and insulin resistance on IVF outcomes where insulin sensitivity was measured using continuous glucose infusion. They found no differences between insulin-resistant and non insulin-resistant women with respect to oocytes collected, implantation rates, pregnancy rates, and OHSS. Obesity, independent of insulin resistance, was associated with lower oocyte count and increased requirement for FSH. Both studies above suggest a relative resistance to FSH stimulation in obese patients with IVF. While diet and weight loss are encouraged, these data do offer some re-assurance to the obese patients. The association of insulin resistance with obesity and ovulatory infertility is well known. Metformin (Glucophage) reduces insulin levels. Metformin dramatically improved ovarian responses in clomiphere resistant patients (4). Stadtmaur et al (5) showed that metformin had a beneficial effect on IVF with clomiphene resistant PCOS patients (BMI >27 kg/m2) with respect to improved mature oocytes, fertilization, embryo cleavage rates, and pregnancy rates. Insulin resistance was measured crudely as a fasting insulin level and there was no difference between the control (Insulin 25.4 μU/ml) and metformin treated group (Insulin 24.2 μU/ml). Regardless, the investigators made the decision to treat with metformin independent of insulin resistance. Thus, it is quite reasonable to have PCOS patients undergoing IVF on metformin. Obesity appears to be a risk factor for early pregnancy loss following ART. Fedorcsak et al (6) showed obese patients had fewer eggs and a higher miscarriage rate in the 1st 6 weeks of pregnancy (12 % versus 22 %, p=0.03), and a lower live birth rate (63 % versus 75 %, p=0.04). Wang et al (7) also showed and increase miscarriage in obese PCOS patients undergoing IVF, 25 % versus 18 % in non-PCOS patients. While not all studies are in agreement, obesity appears to play some role in ART outcome. Weight loss has been shown to be beneficial for reproductive outcomes (Clark et al (8) and should be encouraged.

References:

1. Hirsch J, Salans L, Aronne LJ. Obesity. In Principles and Practice of Endocrinology and Metabolism, 3rd ed. K. Beckers, Ed. 2001. Lippencott Williams and Wilkens, Philadelphia, pp1239-1240.

2. Lashen H, Ledger W, Bernal AL, Barlow D. Extremes of body mass do not adversely affect the outcome of superovulation and in-vitro fertilization. 1999 Hum. Reprod. 14(3):712-7151.

3. Ferorcsak P, storing R, Dale PO, Tanbo T, Abyholm T. Obesity is a risk factor for early pregnancy loss after IVF or ICSI. 2000 Acta Obstet Gynecol Scan.79:43-48.

4. Nestler J E, Jakubowitz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. 1998. NEJM 338:1976-1880.

5. Stadtmaur LA, Toma SK, Riehl RM, Talbert LM. Metformin treatment of patients with polycystic ovarian syndrome indergoing in vitro fertilization improves outcomes and is associated with modulation of insulin-like growth factors. 2001. Fertil. Steril. 75:505-509.

6. Fedorcsak P, storing R, Dale PO, Tanbo T, Abyholm T. Obesity is a risk factor for early pregnancy loss after IVF or ICSI. 2000 Acta Obstet Gynecol Scan.79:43-48.

7. Wang JX, Davies MJ, Norman RJ. Polycystic ovarian syndrome and the risk of spontaneous abortion following assisted reproductive technology treatment. 2001. Hum. Repro. 16(12);2606-2609.

8. Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. 1998. Hum. Repro. 13(6):1502-1505
 

 

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