Abstract
Purpose
The association between obesity and reproductive outcome is controversial. The aim of this study is to evaluate the effects of obesity on clinical pregnancy rates following transfer of a single fresh embryo.
Methods
A retrospective cohort study was conducted at a single tertiary medical center, including all first, fresh, single-embryo transfers using non-donor oocytes, during 2008–2013. We compared clinical pregnancy rate and pregnancy outcomes of singleton live births resulting from the transfer of a single fresh embryo in normal weight, overweight, and obese women, defined as body mass index (BMI) < 25 kg/m2, ≥ 25 BMI <30 kg/m2, and BMI ≥ 30 kg/m2, respectively.
Results
Overall, 1345 cases met the inclusion criteria with 864 single-embryo transfers (SETs) in normal weight women, 292 in overweight women, and 189 SETs in obese women, resulting in 538 clinical pregnancies and 354 singleton births. The clinical pregnancy rate per transfer was similar among the three groups (41.3, 37.6, 37.5%, respectively, p = 0.416). Similarly, there were no significant differences in live births or ongoing pregnancies. On multivariate logistic regression analysis, BMI did not impact the likelihood for clinical pregnancy (OR 0.98, 95% CI 0.96–1.008, p = 0.216).
Conclusions
Our study demonstrated that obesity has no detrimental effect on the clinical pregnancy rate resulting from the transfer of a single fresh embryo.
Keywords: Single-embryo transfer, In vitro fertilization, Obesity, Pregnancy complications
Introduction
Obesity is a universal health problem. In some countries, over 50% of reproductive aged women are either overweight (body mass index (BMI) 25–29.9 kg/m2) or obese (BMI ≥ 30 kg/m2) [1–3]. Compared to normal weight women (BMI 18.5–24.9 kg/m2), obese women have a threefold risk for infertility [4, 5]. In addition, obesity is associated with increased risk for poor obstetrical outcome, including miscarriage, preeclampsia, gestational diabetes, induction of labor, operative delivery, fetal macrosomia, and congenital anomalies [6–8].
The effect of BMI on the outcome of in vitro fertilization (IVF) remains unclear. Although some authors have reported no negative effects of obesity on IVF outcome [9, 10], others have directly linked overweight and obesity to an adverse outcome. This includes the need for increased dose of gonadotropins, reduced number of oocytes collected, a high cancelation rate, and reduced pregnancy and live birth rates [11, 12].
Most studies that evaluated the impact of BMI on IVF outcome included transfer of multiple embryos at various stages of development, including more than 1 cycle per woman, and did not adjust for potential confounders [13, 14]. Recently, the trend towards SET has been increasing in order to minimize the risk for multiple gestations. While some studies showed a significantly lower live birth rate with a single cycle of SET versus a single cycle of double embryo transfer [15], others did not find any differences in the pregnancy rate [14].
The aim of our study was to evaluate the impact of obesity on clinical pregnancy rate following single-embryo transfers (SET) in fresh IVF cycles in young women.
Materials and methods
We conducted a retrospective study at the reproductive unit of the McGill University Health Center in Montreal, Quebec, Canada, evaluating SETs performed between December 2008 and December 2013. All first, fresh, SETs using non-donor oocytes in women ≤ 40 years old were included in the study. A woman was only included once. The study was approved by the institutional research and ethics board (Study 12-283-SDR).
We retrieved the data from our continuously updated computerized database, cross-checked with the patient’s medical file. A detailed telephone survey was conducted by trained personnel to obtain missing information. The change in the Quebec policy for public funding of assisted reproductive technology in August 2010 expedited SETs, where SET is the rule apart for exceptional cases. We compared cycle outcome and singleton live birth outcomes of SET in non-obese and obese women. The BMI was measured for each woman prior to hormonal stimulation and calculated as weight in kilograms divided by the square of height in meters (kg/m2).
The primary outcome was clinical pregnancy rate, defined as intrauterine gestational sac with embryonic pole with fetal heartbeat on transvaginal ultrasound. The secondary outcomes included live birth rates and neonatal and maternal outcomes in cases with live birth. Neonatal outcome included birth weight, small for gestational age (SGA), and large for gestational age (LGA), defined as birth weight < 10th percentile and > 90th percentile for gestational age, respectively, according to the Canadian live born infant birth weight curves [16], congenital malformations, admission to the neonatal intensive care unit, and respiratory and gastrointestinal complications.
Maternal adverse outcome included preeclampsia [International Classification of Diseases (ICD) 10 codes O.14, O.15], placenta previa (ICD 10 code O.44), placental abruption (ICD 10 code O.45), chorioamnionitis (according to placental pathology reports), and gestational diabetes (ICD code O.24.4).
Other variables collected were maternal and paternal age, gravidity and parity, and type of protocol used (microdose flare, fixed antagonist, a mid-luteal long agonist protocol, or a natural-cycle IVF with no gonadotropin stimulation). Etiology of infertility was divided into six major categories: unexplained infertility, tubal factor infertility, endometriosis (laparoscopy or ultrasound findings of ovarian endometrioma were required for diagnosis), male infertility, polycystic ovarian syndrome, or poor ovarian response or reserve [17].
Embryo transfer day was determined based on the quantity and quality of embryos. All embryos were cultured in cleavage medium (Cook Medical, Sydney, Australia) until day 3, then transferred to blastocyst medium (Cook Medical, Sydney, Australia) for further culture to the blastocyst stage, when appropriate. All embryo cultures were performed under low-oxygen conditions (5% oxygen, 6% carbon dioxide, 89% nitrogen). Cleavage embryos were graded as good quality if they had four cells on day 2 or seven to eight cells on day 3, < 20% fragmentation, and exhibited no apparent morphological abnormalities [18]. Cleavage embryos were graded as good quality if they had four cells on day 2 or seven to eight cells on day 3, < 20% fragmentation, and exhibited no apparent morphological abnormalities [18]. Blastocysts were graded according to the level of expansion, the presence and the quality of inner cell mass, and quality of trophectoderm. Top quality blastocysts were defined as ≥ 3 blastocysts with inner cell mass loosely grouped with several cells and few trophectoderm cells forming a loose epithelium based on the Gardner and Schoolcraft scoring system [19]. The patients’ age and the number and quality of cleavage embryos determined the allocation to blastocyst versus cleavage transfer. Ultrasound-guided embryo transfer was performed, and a serum beta human chorionic gonadotropin pregnancy (beta-hCG) test was performed 16 days after collection.
Statistical analysis was performed using SPSS version 21. Patient characteristics and clinical outcomes were tabulated into three BMI categories: normal weight, overweight, and obese women, defined as body mass index (BMI) < 25 kg/m2, ≥ 25 BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Univariate analysis included chi-squared test for categorical variables and analysis of variants for continuous variables. To evaluate the effect of obesity on the clinical pregnancy rate, a multivariate logistic regression analysis was performed controlling for BMI and other confounders known to affect pregnancy rates (maternal age, smoking, cause of infertility, number of retrieved oocytes, and day of embryo transfer).
Results
The study included a total of 1345 first fresh IVF-SET cycles using non-donor oocytes. Of those, 864 patients were of normal weight, 292 overweight, and 189 were obese women resulting in 538 clinical pregnancies and 354 singleton births. We excluded seven women with monozygotic twins. In addition, 94 patients whose pregnancy outcome could not be traced beyond the first trimester were considered ongoing pregnancies, and as a result, we could not calculate live birth rate per transfer.
Demographics and treatment characteristics of the three study groups are presented in Table 1. Polycystic ovary syndrome (PCOS) was more common in obese women than in overweight and normal weight women (16.3 vs. 6.5 and 5.6%, respectively. p = 0.001). Women of normal weights had a significantly shorter duration of stimulation and a lower total dose of FSH compared to overweight and obese women, with no significant difference in the number of retrieved oocytes (Table 1).
Table 1.
Demographic and treatment parameters of the study groups
| Variables | Normal weight BMI < 25 N = 864 |
Overweight ≥ 25 BMI < 30 N = 292 |
Obese BMI ≥ 30 N = 189 |
p value |
|---|---|---|---|---|
| BMI (mean) | 21.5 ± 1.9 | 27 ± 1.3 | 35.3 ± 4.7 | < 0.001 |
| Age (years) | 34.4 ± 4.1 | 34.2 ± 4.6 | 34.7 ± 4.2 | 0.528 |
| Primary infertility | 857/864 (99.2) | 291/292 (99.3) | 187/189 (98.9) | 0.905 |
| Causes of infertility | ||||
| PCOS (%) | 23/409 (5.6) | 9/138 (6.5) | 14/86 (16.3) | 0.094 |
| Male (%) | 156/409 (38.1) | 61/138 (44.2) | 36/86 (41.9) | |
| Unexplained (%) | 131/409 (32) | 41/138 (29.7) | 17/86 (19.8) | |
| Mechanical (%) | 32/409 (7.8) | 16/138 (11.6) | 8/86 (9.3) | |
| Endometriosis (%) | 31/409 (7.6) | 1/138 (0.7) | 5/86 (5.8) | |
| Poor ovarian reserve (%) | 25/409 (6.1) | 7/138 (5.1) | 5/86 (5.8) | |
| Anovulation (%) | 11/409 (20.7) | 3/138 (2.2) | 1/86 (1.2) | |
| Smoking status (%) | 32/409 (7.8) | 20/138 (14.4) | 10/86 (11.6) | 0.056 |
| Duration of stimulation (days) | 16.4 ± 4.2 | 17.3 ± 5.4 | 17.0 ± 3.9 | 0.007 |
| Total HMG used (units) | 1616 ± 1418 | 1778 ± 1525 | 1722 ± 1310 | 0.424 |
| Total FSH used (units) | 2231 ± 1746 | 2603 ± 1695 | 2535 ± 1304 | 0.004 |
| Antagonist protocol | 526 (60.9) | 152 (52.1) | 113 (59.8) | 0.185 |
| Number of retrieved oocytes | 10.4 ± 6.3 | 10.6 ± 6.7 | 10.0 ± 6.2 | 0.592 |
| Assisted hatching | 195 (22.6) | 72 (24.7) | 35 (18.5) | 0.286 |
| Embryo transfer day 5 | 545 (63) | 178 (60.9) | 111 (58.7) | 0.264 |
Data is presented as n (%)
Table 2 summarizes the overall cycle outcome; no significant differences were found in the clinical pregnancy rate between normal weight, overweight, and obese women (p = 0.416). Table 3 summarizes the pregnancy outcomes of clinical pregnancies; there were no significant differences in live births or ongoing pregnancies among the three groups (p = 0.706, p = 0.624, respectively).
Table 2.
Cycle outcome of women after single-embryo transfer
| Cycle outcome | Normal weight BMI < 25 N = 864 |
Overweight ≥ 25 BMI < 30 N = 292 |
Obese BMI ≥ 30 N = 189 |
p value |
|---|---|---|---|---|
| Biochemical pregnancy | 57 (6.5) | 20 (6.8) | 8 (4.2) | 0.456 |
| Clinical pregnancy rate | 357 (41.3) | 110 (37.6) | 71 (37.5) | 0.416 |
| Ectopic pregnancy | 3 (0.3) | 0 | 1 (0.5) | 0.526 |
| Not pregnant | 447 (51.7) | 162 (55.4) | 109 (57.6) | 0.283 |
Data is presented as n (%)
Table 3.
Pregnancy outcomes of clinical pregnancies in women after single-embryo transfer
| Cycle outcome | Normal weight BMI < 25 N = 357 |
Overweight ≥ 25 BMI < 30 N = 110 |
Obese BMI ≥ 30 N = 71 |
p value |
|---|---|---|---|---|
| Live birthsa | 231 (64.7) | 73 (66.3) | 50 (70.4) | 0.706 |
| Miscarriages | 57 (16) | 13 (11.8) | 11(15.5) | 0.601 |
| Stillbirths | 3 (0.8) | 2 (1.8) | 1(1.4) | 0.673 |
| Termination of pregnancies | 2 (0.6) | 1(0.9) | 0 | 0.725 |
| Ongoing pregnanciesb | 64 (17.9) | 21 (19.2) | 9(12.6) | 0.624 |
Data is presented as n (%)
aKnown live births calculated clinical pregnancy
bOngoing pregnancy beyond the first trimester
Pregnancy outcomes in cases with singleton live births are presented in Table 4. Maternal characteristics were similar among the groups. There were no significant differences in mean birth weight, gestational age, SGA, or preterm delivery among the three groups. There was a lower rate of preeclampsia in normal weight women compared with overweight and obese women (p = 0.026).
Table 4.
Pregnancy outcomes and complications in cases with live births after the transfer of a single embryo stratified by BMI groups
| Pregnancy outcome | Normal weight BMI < 25 N = 231 |
Overweight ≥ 25 BMI < 30 N = 73 |
Obese BMI ≥ 30 N = 50 |
p value |
|---|---|---|---|---|
| Maternal age | 33.2 ± 3.6 | 32.7 ± 4.2 | 34.1 ± 4.0 | 0.131 |
| Paternal age | 36.5 ± 5.8 | 37.1 ± 6.3 | 37.2 ± 5.6 | 0.693 |
| BMI | 21.3 ± 2.0 | 27.0 ± 1.4 | 34.3 ± 3.9 | < 0.0001 |
| Smoking | 14/221 | 11/71 | 5/49 | 0.056 |
| Primary infertility | 224(96.9) | 71(97.2) | 48 (96) | 0.919 |
| ICSI | 167 (72.2) | 59 (80.8) | 43 (86) | 0.153 |
| Embryo transfer day 5 (%) | 185 (80) | 61 (83.5) | 42 (84) | 0.701 |
| Etiology of infertility | n = 223 | n = 73 | n = 48 | 0.276 |
| PCOS (%) | 17(7.6) | 7 (8.2) | 8 (16.7) | |
| Male infertility (%) | 95 (42.6) | 35 (47.9) | 21 (43.8) | |
| Tubal factor infertility (%) | 20 (9) | 10 (13.7) | 6 12.5) | |
| Endometriosis (%) | 14 (6.3) | 0 | 2 (4.1) | |
| Poor ovarian reserve (%) | 12 (5.4) | 4 (5.5) | 3 (6.3) | |
| Unexplained (%) | 65 (29.1) | 17 (23.3) | 8 (16) | |
| Gestational age at delivery (weeks) | 37.9 ± 2.8 | 38.2 ± 2.6 | 37.9 ± 2.1 | 0.782 |
| Birth weight (g) | 3117 ± 682 | 3297 ± 682 | 3202 ± 542 | 0.135 |
| Male gender | 112 (50.7) | 30 (42.9) | 21(47.7) | 0.517 |
| C/S | 88 (38.1) | 22 (30.1) | 21/50 (42) | 0.642 |
| SGA | 22/222 (9.9) | 7/70 (10) | 3/44 (6.8) | 0.559 |
| PTD | 36/222 (16.2) | 9/70 (12.9) | 6/44 (13.6) | 0.497 |
| Preeclampsia | 3/222 (1.3) | 5/70 (7.1) | 3/44 (6.8) | 0.026 |
| Placental abruption | 3 (1.3) | 1 (1.4) | 0 | 0.716 |
| Gestational diabetes | 3 (1.3) | 0 | 2(4.0) | 0.176 |
| LGA | 11/222 (5) | 7/70 (10) | 2/44 (4.5) | 0.293 |
| Chorioamnionitis | 3 (1.3) | 0 | 2 (4.0) | 0.176 |
| Genetic disorder/malformation | 3/222 (1.4) | 0 | 0 | 0.438 |
| Maternal complications | 19 (8.2) | 9 (12.3) | 7(14) | 0.341 |
| Neonatal complications | 74(32) | 23(31.5) | 11 (22) | 0.369 |
| Any maternal or neonatal complication | 84/221 (38) | 25/70 (35.7) | 15/44 (34.1) | 0.858 |
For all variables, categorical data is presented as n (%) and continuous variables are presented as mean ± SD
BMI body mass index (at the start of infertility treatment), ICSI intracytoplasmic sperm injection, PCOS polycystic ovarian syndrome, C/S cesarean section, SGA small for gestational age (< 10%), PTD preterm delivery (< 37 weeks), LGA large for gestational age (> 90%)
After adjustment for potential confounders including BMI, maternal age, smoking, etiology of infertility, number of retrieved oocytes, and day of embryo transfer, obesity was not found to be an independent variable associated with lower rates of clinical pregnancies (Table 5). Day of transfer (cleavage stage vs. blastocyst stage) and maternal age were found to be independently associated with clinical pregnancies (OR 0.96, 95% CI 0.93–0.99, p = 0.015 and OR 0.29, 95% CI 0.22–0.38, p < 0.001, respectively). On stepwise, forward likelihood ratio analysis, day 3 embryo transfer (vs. day 5) was a significant negative predictor of clinical pregnancies (OR 0.38, 95% CI 0.25–0.57, p < 0.001).
Table 5.
Multivariate logistic regression analysis for clinical pregnancies as a dependent variable
| Variable | OR (95% CI) | P value |
|---|---|---|
| BMI | 0.98 (0.96–1.01) | 0.22 |
| Age | 0.96 (0.93–0.99) | 0.01 |
| Number of retrieved oocytes | 1.014 (0.99–1.03) | 0.17 |
| Smoking | 0.86 (0.76–1.35) | 0.13 |
| Day 3 vs. day 5 transfer | 0.29 (0.22–0.38) | < 0.001 |
BMI body mass index (at the start of infertility treatment)
Discussion
In this study, we evaluated the effect of obesity on clinical pregnancy rate following transfer of a single fresh embryo. Our key findings are as follows: (1) Obesity did not affect the clinical pregnancy rate, number of live births, or ongoing pregnancies following the transfer of a single fresh embryo; (2) pregnancy outcome and obstetric complications were similar among normal weight, overweight, and obese women, apart for a lower rate of preeclampsia in normal weight women; and (3) younger maternal age and day 5 embryo transfer were the only significant factors associated with higher rates of clinical pregnancies.
Previous studies that addressed the correlation between obesity and reproductive outcomes have been controversial. Some studies reported decreased implantation and pregnancy rates, increased miscarriage rates, and poor pregnancy outcomes in obese women [7, 11, 13]. Those unfavorable outcomes have been attributed to multiple factors including adverse effects of obesity on oocyte and embryo quality, poor ovarian response necessitating increased gonadotropin injections, and lower numbers of collected oocytes [20, 21], as well as impaired endometrium [22]. However, other studies using the donor-oocyte recipient model have not found any association between increased BMI and reduced pregnancy rate or increased miscarriage rate [23].
Systematic reviews have concluded that obese women have a lower likelihood of pregnancy and live birth with an increased risk of miscarriage. However, there is insufficient evidence whether this affects cycle cancelation and oocyte recovery rates [14]. Cases included in those reviews had considerable clinical and methodological heterogeneity in the transfer of multiple embryos and transfer of fresh or frozen embryos, with an inconsistent adjustment for risk factors. Studies on single-embryo transfers showed that obesity was negatively associated with the occurrence of live birth [24]. A retrospective study found that morbid obesity significantly increased miscarriage rates and reduced live birth rates [25]. However, in contrast to our research, their study included only blastocyst transfer and fresh and frozen embryos.
The results of our study showed that the clinical pregnancy rates resulting from transfer of fresh SET were comparable in normal weight, overweight, and obese women and that increased BMI was not associated with increased adverse obstetric and perinatal outcome. These findings remained negative after adjusting for potential confounders. Our results are consistent with a previous study performed based on the Latin American Registry that found no association between overweight and obesity and the likelihood of pregnancy, live birth, or miscarriage in women undergoing assisted reproductive technology [26]. Similarly, Insogna et al. [27] reported no impact of BMI on implantation rates or clinical pregnancy rates in frozen-thawed blastocyst transfer. Nonetheless, the lack of statistical differences in our study could also be due to the possibility of type I statistical error.
Previous studies that examined the impact of obesity on obstetric outcome have demonstrated increased risk for adverse outcome including preeclampsia, gestational diabetes, operative delivery, and more [6, 7]. In our study, we did not find any differences in maternal and neonatal outcome between obese and overweight women, though normal weight women had a lower rate of preeclampsia in comparison.
The only independent factors found to be associated with increased clinical pregnancy rate were maternal age and day of embryo transfer. While this was not the primary outcome of our study, it is an important finding. As previous studies have shown, blastocyst embryo transfer is associated with increased implantation and live birth rate compared to cleavage-stage embryo transfer [28, 29]. In our study, this finding remained significant even after adjusting for potential confounders including BMI.
The main limitation of our study lies in its retrospective design and the inherent risk for undetected selection bias. Furthermore, we did not have data regarding other potential confounders such as ethnicity, prior obstetrical complications, and family history. We used Canadian population growth curves to assess the rate of SGA (< 10% percentile) to mitigate the lack of ethnicity data. Over 80% of our populations were nulliparous women, thereby minimizing the potential effect of previous pregnancy complications on pregnancy outcome. Moreover, while pregnancy outcome and obstetric complications were similar among normal weight, overweight, and obese women, the groups might be too small to draw definite conclusions and large-scale studies are needed.
The strengths of our study are these were singletons as a result of the transfer of a single embryo performed in a single-center study with a SET policy for all patients, thus minimizing the bias of good-prognosis patient selection and without the possibility of a deleterious effect of the vanishing twin phenomenon on the pregnancy outcome. Furthermore, the same culture media was used, eliminating the possible different effects of various culture media on the subsequent neonatal outcome [30]. Finally, we included only fresh embryos to minimize any potential effects attributed to freeze-thawed embryos [31]. Our findings can be used to reassure physicians in our field that the transfer of a single fresh embryo in obese women should result in similar implantation and pregnancy rates compared to transfers in normal weight and overweight women. Obesity does not appear to be associated with increased adverse obstetric and perinatal outcomes in this subset population.
In conclusion, our study demonstrates that obesity does not impact the clinical pregnancy rates resulting from the transfer of a single fresh embryo.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Footnotes
Avi Ben-Haroush and Ido Sirota contributed equally to this work.
References
- 1.Deitel M. The international obesity task force and “globesity”. Obes Surg. 2002;12(5):613–614. doi: 10.1381/096089202321019558. [DOI] [PubMed] [Google Scholar]
- 2.Balen AH, Anderson RA. Impact of obesity on female reproductive health: British fertility society, policy and practice guidelines. Hum Fertil. 2007;10(4):195–206. doi: 10.1080/14647270701731290. [DOI] [PubMed] [Google Scholar]
- 3.Bellver J, Ayllón Y, Ferrando M, Melo M, Goyri E, Pellicer A, Remohí J, Meseguer M. Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertil Steril. 2010;93(2):447–454. doi: 10.1016/j.fertnstert.2008.12.032. [DOI] [PubMed] [Google Scholar]
- 4.Van Der Steeg JW, Steures P, Eijkemans MJC, et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod. 2008;23(2):324–328. doi: 10.1093/humrep/dem371. [DOI] [PubMed] [Google Scholar]
- 5.Brewer CJ, Balen AH. The adverse effects of obesity on conception and implantation. Reproduction. 2010;140(3):347–364. doi: 10.1530/REP-09-0568. [DOI] [PubMed] [Google Scholar]
- 6.Linné Y. Effects of obesity on women’s reproduction and complications during pregnancy. Obes Rev. 2004;5(3):137–143. doi: 10.1111/j.1467-789X.2004.00147.x. [DOI] [PubMed] [Google Scholar]
- 7.Catalano PM, Ehrenberg HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG. 2006;113(10):1126–1133. doi: 10.1111/j.1471-0528.2006.00989.x. [DOI] [PubMed] [Google Scholar]
- 8.Stothard KJ, Tennant PWG, Bell R. Maternal overweight and obesity and the risk of congenital anomalies. Heal San Fr. 2009;301(6):636–650. doi: 10.1001/jama.2009.113. [DOI] [PubMed] [Google Scholar]
- 9.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. doi: 10.1016/j.ejogrb.2005.12.009. [DOI] [PubMed] [Google Scholar]
- 10.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):706–711. doi: 10.1016/j.rbmo.2010.06.040. [DOI] [PubMed] [Google Scholar]
- 11.Fedorcsák P, Dale PO, Storeng R, Ertzeid G, Bjercke S, Oldereid N, Omland AK, Abyholm T, Tanbo T. Impact of overweight and underweight on assisted reproduction treatment. Hum Reprod. 2004;19(11):2523–2528. doi: 10.1093/humrep/deh485. [DOI] [PubMed] [Google Scholar]
- 12.Fedorcsák P, Storeng R, Dale PO, Tanbo T, Abyholm T. Obesity is a risk factor for early pregnancy loss after IVF or ICSI. Acta Obstet Gynecol Scand. 2000;79(1):43–48. doi: 10.1080/j.1600-0412.2000.079001043.x. [DOI] [PubMed] [Google Scholar]
- 13.Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008;90(3):714–726. doi: 10.1016/j.fertnstert.2007.07.1290. [DOI] [PubMed] [Google Scholar]
- 14.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):421–439. doi: 10.1016/j.rbmo.2011.06.018. [DOI] [PubMed] [Google Scholar]
- 15.Pandian Z, Marjoribanks J, Ozturk O, Serour G, Bhattacharya S. Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection: summary of a Cochrane review. Fertil Steril. 2014;102(2):345–347. doi: 10.1016/j.fertnstert.2014.04.029. [DOI] [Google Scholar]
- 16.Kramer MS, Platt RW, Wen SW, Joseph KS, Allen A, Abrahamowicz M, Blondel B, Bréart G, Fetal/Infant Health Study Group of the Canadian Perinatal Surveillance System A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics. 2001;108(2):e35. doi: 10.1542/peds.108.2.e35. [DOI] [PubMed] [Google Scholar]
- 17.Ferraretti AP, La Marca A, Fauser BCJM, Tarlatzis B, Nargund G, Gianaroli L. ESHRE consensus on the definition of poor response to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26(7):1616–1624. doi: 10.1093/humrep/der092. [DOI] [PubMed] [Google Scholar]
- 18.Reinblatt SL, Ishai L, Shehata F, Son WY, Tulandi T, Almog B. Effects of ovarian endometrioma on embryo quality. Fertil Steril. 2011;95(8):2700–2702. doi: 10.1016/j.fertnstert.2011.03.002. [DOI] [PubMed] [Google Scholar]
- 19.Gardner DK, Surrey E, Minjarez D, Leitz A, Stevens J, Schoolcraft WB. Single blastocyst transfer: a prospective randomized trial. Fertil Steril. 2004;81(3):551–555. doi: 10.1016/j.fertnstert.2003.07.023. [DOI] [PubMed] [Google Scholar]
- 20.Wittemer C, Ohl J, Bailly M, Bettahar-Lebugle K, Nisand I. Does body mass index of infertile women have an impact on IVF procedure and outcome? J Assist Reprod Genet. 2000;17(10):547–552. doi: 10.1023/A:1026477628723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Norman RJ, Chura LR, Robker RL. Effects of obesity on assisted reproductive technology outcomes. Fertil Steril. 2008;89(6):1611–1612. doi: 10.1016/j.fertnstert.2007.02.065. [DOI] [PubMed] [Google Scholar]
- 22.Bellver J, Pellicer A, García-Velasco JA, Ballesteros A, Remohí J, Meseguer M. Obesity reduces uterine receptivity: clinical experience from 9,587 first cycles of ovum donation with normal weight donors. Fertil Steril. 2013;100(4):1050–1058. doi: 10.1016/j.fertnstert.2013.06.001. [DOI] [PubMed] [Google Scholar]
- 23.Wattanakumtornkul S, Damario MA, Stevens Hall SA, Thornhill AR, Tummon IS. Body mass index and uterine receptivity in the oocyte donation model. Fertil Steril. 2003;80(2):336–340. doi: 10.1016/S0015-0282(03)00595-8. [DOI] [PubMed] [Google Scholar]
- 24.Sifer C, Herbemont C, Adda-Herzog E, et al. Clinical predictive criteria associated with live birth following elective single embryo transfer. Eur J Obstet Gynecol Reprod Biol. 2014;181:229–232. doi: 10.1016/j.ejogrb.2014.08.004. [DOI] [PubMed] [Google Scholar]
- 25.Russo M, Ates S, Shaulov T, Dahan MH. Morbid obesity and pregnancy outcomes after single blastocyst transfer: a retrospective, north American study. J Assist Reprod Genet. 2017;34(4):451–457. doi: 10.1007/s10815-017-0883-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.MacKenna A, Schwarze JE, Crosby JA, Zegers-Hochschild F. Outcome of assisted reproductive technology in overweight and obese women. JBRA Assist Reprod. 2017;21(2):79–83. doi: 10.5935/1518-0557.20170020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Insogna IG, Lee MS, Reimers RM, Toth TL. Neutral effect of body mass index on implantation rate after frozen-thawed blastocyst transfer. Fertil Steril. 2017;99(2):389–392. doi: 10.1016/j.fertnstert.2017.08.024. [DOI] [PubMed] [Google Scholar]
- 28.Glujovsky D, Farquhar C, Quinteiro Retamar AM, Alvarez Sedo CR, Blake D. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev. 2016. 10.1002/14651858.CD002118.pub5. [DOI] [PubMed]
- 29.George K, Mangalraj A, Muthukumar K, Aleyamma T, Kamath M. Blastocyst stage transfer vs cleavage stage embryo transfer. J Hum Reprod Sci. 2009;2(1):23–26. doi: 10.4103/0974-1208.51339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Dumoulin JC, Land JA, Van Montfoort AP, et al. Effect of in vitro culture of human embryos on birthweight of newborns. Hum Reprod. 2010;25(3):605–612. doi: 10.1093/humrep/dep456. [DOI] [PubMed] [Google Scholar]
- 31.Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2012;98(2):368–377. doi: 10.1016/j.fertnstert.2012.05.019. [DOI] [PubMed] [Google Scholar]