Does obesity have detrimental effects on IVF treatment outcomes?

Between January of 2008 and October of 2013, a total of 1620 IVF-ICSI cycles were carried out at the infertility clinic of the Gulhane Military Academy. Records of the subjects following their first IVF-ICSI cycles were analyzed, and of these, 320 embryo transfer cycles fulfilled our inclusion criteria: (i) women ≤ 38 years of age, (ii) cycles arising from single embryo transfer (SET) or double embryo transfer (DET), and (iii) where the data on the outcome was available. Cycles arising from more than two embryo transfers (ETs) and cryo-thaw embryos were excluded from the analyses.

This study was approved by the institutional review board of the Gulhane Military Academy (approval number 2013/168.4-2543). Since this was a retrospective cohort study, no written informed consent for participation was obtained from the participants. The patients underwent IVF according to standard stimulation protocols, involving pituitary down-regulation with either a GnRH agonist administered in the mid-luteal phase of the prior cycle (long protocol), or a diluted GnRH agonist given on days 2–4 of the cycle (micro-dose protocol). Alternatively, a short protocol with a GnRH antagonist was started when the leading follicle reached 14 mm. Controlled ovarian stimulation was achieved with hMG and/or recombinant FSH. The response to stimulation was monitored using serum E2 and a transvaginal ultrasound. Human chorionic gonadotropin (hCG) was administered to stimulate the final stages of follicular development when the follicles reached maturity, defined by two leading follicles over 18 mm. A transvaginal follicle aspiration was performed 36 h after hCG administration, and the embryo transfer took place 48 h later. Micronized vaginal progesterone, at daily dose of 600 mg, was used for 2 weeks for luteal support.

The embryos were transferred to the uterus either 3 days (cleavage stage) or 5 days (blastocyst stage) after the oocyte retrieval, and the embryo quality was assessed on the day of transfer. The cleavage stage embryos were scored based on cell number and the degree of fragmentation, according to the grading system of Hardarson (2001) [12]. The embryos at an appropriate developmental stage, with <20 % fragments and a mild degree of uneven-sized blastomeres (grade I, grade IIA, and grade IIB), constituted the day-3 embryos that were suitable for transfer. In the case of extended culture, all of the blastocyst stage embryos were evaluated using the grading system of Gardner and Schoolcraft (1994). The blastocysts were graded according to the degree of expansion, and the quality of the inner cell mass and trophoectoderm [13]. The grade III–VI embryos, according to blastocyst expansion and hatching status, with an inner cell mass and trophoectoderm grades of A or B constituted the day-5 embryos suitable for transfer. The total number of embryos suitable for ET (either at the cleavage or blastocyst stage) was calculated for each patient.

At day 12 of the ET, each patient had her β-hCG levels assessed. Pregnancy was defined by serially increasing serum β-hCG titres to at least 25 IU/l, within 12 days after the cleavage stage ET. All of the patients underwent transvaginal ultrasounds at 5 to 6 weeks of gestation, or when the β-hCG exceeded 2,000 IU/L, in order to determine the location and number of the pregnancies. Biochemical pregnancy was defined as a transient pregnancy that spontaneously resolved before the ultrasonographic confirmation. Clinical pregnancy was documented by ultrasonographic evidence of the fetal cardiac activity at 6–7 weeks of gestation. Spontaneous abortion was defined as the loss of a clinical pregnancy. Additionally, ongoing pregnancy was defined as progression beyond 12 weeks of gestation.

The patients’ age, infertility duration-etiology, antral follicle count, baseline FSH, LH, and estradiol levels (cycle day 3) were reviewed. The IVF-ICSI cycle characteristics, including the total gonadotropin dose used, duration of stimulation, number of retrieved oocytes, metaphase 2 (MII) oocytes, proportion of oocytes fertilized, and embryo quality were noted. The women were assessed for polycystic ovary syndrome (PCOS) as defined by the 2003 Rotterdam European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine sponsored PCOS consensus workshop group [14]. The BMI was calculated by using the formula weight/height² from the medical records. According to the World Health Organization (WHO) guidelines, the women were grouped into three categories, namely normal: 18.5–24.9 kg/m²; overweight: 25–29.9 kg/m²; obese: ≥30 kg/m². Because the number of women in underweight group (BMI <18.5 kg/m²) was low (n = 22), these patients were excluded from the analysis.

The data were analyzed using the Microsoft Statistical Package for the Social Sciences (SPSS) for Windows, version 22.0. The Kruskal-Wallis test was conducted to explore the differences among the BMI categories, while the Mann-Whitney U test was conducted to analyze the continuous and discrete ordinal variables, and the nominal data was analyzed using the χ² test. All of the Mann-Whitney U and χ² tests were two tailed, and Bonferroni’s correction was used to adjust for multiple comparisons, unless otherwise stated. The potential correlation between the BMI, total gonadotropin dose, stimulation duration, and IVF-ICSI treatment outcomes was evaluated using the Spearman Rank Order Correlation. Finally, multiple regression analyses were used to assess the variables for the total gonadotropin dose and stimulation duration. Preliminary analyses were conducted to ensure no violation of the assumptions of normality, linearity, multicollinearity, and homoscedasticity. A P value of <0.05 was considered to be statistically significant.

1. WHO. Obesity and overweight, Fact Sheet 311. Geneva: World Health Organization; 2006.Google Scholar
2. Tesauro M, Canale MP, Rodia G, Di Daniele N, Lauro D, Scuteri A, et al. Metabolic syndrome, chronic kidney, and cardiovascular diseases: role of adipokines. Cardiol Res Pract. 2011;653182.Google Scholar
3. Michels KB, Terry KL, Eliassen AH, Hankinson SE, Willett WC. Adult weight change and incidence of premenopausal breast cancer. Int J Cancer. 2012;130(4):902–9.View ArticlePubMedGoogle Scholar
4. Robker RL. Evidence that obesity alters the quality of oocytes and embryos. Pathophysiology. 2008;15(2):115–21.View ArticlePubMedGoogle Scholar
5. Brewer CJ, Balen AH. The adverse effects of obesity on conception and implantation. Reproduction. 2010;140(3):347–64.View ArticlePubMedGoogle Scholar
6. Aly H, Hammad T, Nada A, Mohamed M, Bathgate S, El-Mohandes A. Maternal obesity, associated complications and risk of prematurity. J Perinatol. 2010;30(7):447–51.View ArticlePubMedGoogle Scholar
7. Bhattacharya S, Campbell DM, Liston WA, Bhattacharya S. Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies. BMC Public Health. 2007;7:168.View ArticlePubMedPubMed CentralGoogle Scholar
8. Rittenberg V, Seshadri S, Sunkara SK, Sobaleva S, Oteng-Ntim E, El-Toukhy T. Effect of body mass index on IVF treatment outcome: an updated systematic review and meta-analysis. Reprod Biomed Online. 2011;23(4):421–39.View ArticlePubMedGoogle Scholar
9. Bellver J, Melo MA, Bosch E, Serra V, Remohí J, Pellicer A. Obesity and poor reproductive outcome: the potential role of the endometrium. Fertil Steril. 2007;88(2):446–51.View ArticlePubMedGoogle Scholar
10. Matalliotakis I, Cakmak H, Sakkas D, Mahutte N, Koumantakis G, Arici A. Impact of body mass index on IVF and ICSI outcome: a retrospective study. Reprod Biomed Online. 2008;16(6):778–83.View ArticlePubMedGoogle Scholar
11. Veleva Z, Tiitinen A, Vilska S, Hydén-Granskog C, Tomás C, Martikainen H, et al. High and low BMI increase the risk of miscarriage after IVF/ICSI and FET. Hum Reprod. 2008;23(4):878–84.View ArticlePubMedGoogle Scholar
12. Hardarson T, Hanson C, Sjögren A, Lundin K. Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation. Hum Reprod. 2001;16(2):313–8.View ArticlePubMedGoogle Scholar
13. Gardner DK, Schoolcraft WB. In vitro culture of human blastocyst. In: Mortimer JR, editor. Toward reproductive certainty: infertility and genetics beyond 1999. Carnforth, UK: Parthenon Press; 1999. p. 378–88.Google Scholar
14. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19–25.View ArticleGoogle Scholar
15. Esinler I, Bozdag G, Yarali H. Impact of isolated obesity on ICSI outcome. Reprod Biomed Online. 2008;17(4):583–7.View ArticlePubMedGoogle Scholar
16. Zhang D, Zhu Y, Gao H, Zhou B, Zhang R, Wang T, et al. Overweight and obesity negatively affect the outcomes of ovarian stimulation and in vitro fertilisation: a cohort study of 2628 Chinese women. Gynecol Endocrinol. 2010;26(5):325–32.View ArticlePubMedGoogle Scholar
17. Farhi J, Ben-Haroush A, Sapir O, Fisch B, Ashkenazi J. High-quality embryos retain their implantation capability in overweight women. Reprod Biomed Online. 2010;21(5):706–11.View ArticlePubMedGoogle Scholar
18. Loh S, Wang JX, Matthews CD. The influence of body mass index, basal FSH and age on the response to gonadotrophin stimulation in non-polycystic ovarian syndrome patients. Hum Reprod. 2002;17(5):1207–11.View ArticlePubMedGoogle Scholar
19. van Swieten EC, van der Leeuw-Harmsen L, Badings EA, van der Linden PJ. Obesity and Clomiphene Challenge Test as predictors of outcome of in vitro fertilization and intracytoplasmic sperm injection. Gynecol Obstet Invest. 2005;59(4):220–4.View ArticlePubMedGoogle Scholar
20. Dokras A, Baredziak L, Blaine J, Syrop C, VanVoorhis BJ, Sparks A. Obstetric outcomes after in vitro fertilization in obese and morbidly obese women. Obstet Gynecol. 2006;108(1):61–9.View ArticlePubMedGoogle Scholar
21. Dechaud H, Anahory T, Reyftmann L, Loup V, Hamamah S, Hedon B. Obesity does not adversely affect results in patients who are undergoing in vitro fertilization and embryo transfer. Eur J Obstet Gynecol Reprod Biol. 2006;127(1):88–93.View ArticlePubMedGoogle Scholar
22. Metwally M, Ledger WL, Li TC. Reproductive endocrinology and clinical aspects of obesity in women. Ann N Y Acad Sci. 2008;1127:140–6.View ArticlePubMedGoogle Scholar
23. Spandorfer SD, Kump L, Goldschlag D, Brodkin T, Davis OK, Rosenwaks Z. Obesity and in vitro fertilization: negative influences on outcome. J Reprod Med. 2004;49(12):973–7.PubMedGoogle Scholar
24. Fedorcsák P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, et al. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod. 2004;19(11):2523–8.View ArticlePubMedGoogle Scholar
25. Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online. 2007;15(5):532–8.View ArticlePubMedGoogle Scholar