High dosage of gonadotropins is associated with increased risk of preterm birth in singletons born after fresh embryo transfer

High dosage of gonadotropins is associated with increased risk of preterm birth in singletons born after fresh embryo transfer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article High dosage of gonadotropins is associated with increased risk of preterm birth in singletons born after fresh embryo transfer Wei Zhou MD, Qianqian Wu, Zhiyi Song, Jiahui Wang, Zijiang Chen Chen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2669191/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Research Question: Does high gonadotropin dosage affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) in singletons born after fresh embryo transfer (ET) cycles? Design: This retrospective cohort study included 12997 singleton births after fresh ET cycles in China from January2013 to December 2020. All women underwent their first IVF/ICSI cycle. Patients were categorized into three groups according to the tertile of total gonadotropin dosage (≤1500 IU, 1501–2100 IU, >2100 IU). Adjusted logistic regression models were performed to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between gonadotropin dosage and the incidence of PTB and LBW. Results: The incidence of PTB and LBW were 6.1% (796/12997) and 4.0% (524/12997), respectively. The incidence of PTB rose from 5.2% (Gn≤1500 IU) to 7.4% (Gn>2100 IU). Compared with the lowest dosage group (≤1500 IU), an elevated incidence of PTB was observed at the highest gonadotropin dosage group (>2100 IU) in adjusted logistic regression model (adjusted OR [aOR]=1.14 [95% CI: 1.04–1.54]). However, the risk of LBW was comparable in three groups. Conclusion: High gonadotropindosage was significantly associated with the increase of PTB risk in singletons born after fresh embryo transfer. Whether mild stimulation regimens using lower dose of gonadotropin could improve pregnancy outcomes needs to be verified in the future studies. fresh embryo transfer gonadotropin dosage preterm birth low birth weight ovarian stimulation Introduction Pregnancies resulting from assisted reproductive technology (ART) are associated with a higher risk of adverse perinatal outcomes such as preterm birth (PTB) and low birth weight (LBW) compared with spontaneous pregnancies. The risk is present both in multiple and singleton pregnancies (McDonald et al., 2009; Pandey, Shetty, Hamilton, Bhattacharya, & Maheshwari, 2012; Pastore & Williams, 2004). However, the reason of increased risk of adverse perinatal outcomes in singleton pregnancies is still not fully understood. The reasons of increased risk of adverse perinatal outcomes in singletons born after IVF/ICSI were multifactorial (McGovern, Llorens, Skurnick, Weiss, & Goldsmith, 2004; Schieve et al., 2002). Previous study indicated that the underlying infertility itself seemed to have a negative impact on perinatal outcomes (Williams, Goldman, Mittendorf, & Monson, 1991). Also, iatrogenic risks of adverse outcomes may come from the in vitro fertilization (IVF) laboratory procedures such as culture time and media composition, freezing/thawing techniques and specific laboratory procedures (Alviggi et al., 2018; Pelkonen et al., 2010; Wang et al., 2005). Moreover, the ovarian stimulation with exogenous gonadotropins may also play a critical role in perinatal outcomes (Klemetti, Sevón, Gissler, & Hemminki, 2010; Pinborg et al., 2013). Superovulation with exogenous gonadotropins is a necessary procedure in ART (Homburg & Insler, 2002; Hughes, 2003). Administration of gonadotropins during ART affects the hormonal milieu at the time of follicular growth and embryos transfer, which may have detrimental effects on embryo development and perinatal outcomes (Evans, Hannan, Hincks, Rombauts, & Salamonsen, 2012; Kelley et al., 2006; M. Mainigi et al., 2016; Santos, Kuijk, & Macklon, 2010; Verberg et al., 2009). More and more study indicated that the ovarian stimulation may be an important factor for adverse perinatal outcomes. Previous studies suggested that stimulated IVF was associated with a higher risk of adverse perinatal outcomes as compared with natural cycle IVF(Kamath, Kirubakaran, Mascarenhas, & Sunkara, 2018; Mak et al., 2016). However, a large dataset showed that there was no significant difference in the risk of PTB and LBW between stimulated and unstimulated IVF (Sunkara, LaMarca, Polyzos, Seed, & Khalaf, 2016). Possible influencing factors of adverse outcomes in ART singletons need to be further explored. Studies focusing on the association between the dosage of exogenous gonadotropins used for ovarian stimulation and perinatal outcomes were rare. The aim of this study was to explore the relationship between gonadotropins dosage and the perinatal outcomes of PTB and LBW in singletons born after fresh embryo transfer. Materials And Methods Study design and participants Anonymous data were obtained from the Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University. This retrospective cohort study included 12997 singleton births from fresh IVF/ICSI cycles with either Day 3 or Day 5 embryo transfer (ET) between January 2013 and December 2020. Women undergoing their first IVF/ICSI cycles because of tubal factors, male factors, ovulatory disorder or others were included. All included women experienced a singleton birth after fresh embryo transfer. Women who had uterine malformations, smoking, using nature cycles in controlled ovarian hyperstimulation (COH), using donor oocytes, conceived multiple pregnancies or vanishing twins were excluded. This study was approved by the ethics committees of Reproductive Medicine Center of Shandong University. Study procedures and outcome The exogenous gonadotropins used for ovarian stimulation included recombinant follicle-stimulating hormone (Puregon, MSD, USA; Gonal-f, Merck Serono, Germany; Urofollitropin for Injection, Livzon Pharmaceutical Group Inc., China; or Recombinant Human Follitropin for Injection, Gensci, China) and urinary human menopausal gonadotropin (Menotrophins for Injection, Livzon Pharmaceutical Group Inc., China; or Menopur, Ferring, Switzerland). The dosage of gonadotropins was adjusted according to the ovarian response. Urinary human chorionic gonadotropin (HCG) at a dose of 4000 to 10,000 IU was used to trigger oocyte maturation when follicles measured 18mm or more. Oocyte retrieval was performed 36 h after the trigger. Day 3 embryos scoring was conducted by the morphologic criteria of Puissant et al.(Puissant, Van Rysselberge, Barlow, Deweze, & Leroy, 1987). And Day 5 embryos were scored according to Gardner morphologic criteria(Gardner, Lane, Stevens, Schlenker, & Schoolcraft, 2000). Luteal-phase support with Duphaston (Abbott, USA) and either Crinone (Merck Serono, Germany) or Utrogestan (Besins Manufacturing Belgium) was initiated immediately after oocyte retrieval and was continued until 10 weeks of gestation. Live-birth was defined as delivery of a viable neonate at 28 weeks or more of gestation. Occurrence of a live-birth at <37 weeks of gestation was defined as PTB. Birthweight 2100 IU). Inter-group difference of baseline characteristics was compared using Wilcoxon rank-sum test for non-normally distributed continuous variables and Chi-squared analysis for categorical variables. Adjusted logistic regression models were performed to evaluate the relationship between the exogenous gonadotropins dose and the risks of PTB and LBW. Based on our univariate analysis, the following variables differed within three Gonadotropin groups and also significantly associated with the risk of PTB or LBW were considered as potential confounders: maternal age, body mass index (BMI), parity, stage of embryo transferred and ovarian stimulation protocol. P-value of <0.05 was considered statistically significant. Analyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC, USA). Results A total of 12997 patients had singleton live-births after their first fresh IVF/ICSI embryo transfer (ET) cycle. Clinical characteristics, cycle parameters and perinatal outcomes are presented in Table I. The mean gonadotropin dosage was 1991.0±926.9 IU. Women using higher gonadotropin dosage were older and had a higher BMI level. The overall incidence of PTB and LBW were 6.1% (796/12997) and 4.0% (524/12997), respectively. The gestational week of PTB patients was 34.4±2.1 weeks. The mean birth weight for PTB infants was 2.0±0.4 kg. Table 2 showed that gonadotropins dosage is positively associated with the incidence of PTB: 5.2% (255/4903) in group 1 (Gn≤1500 IU), 5.8% (232/3892) in group 2 (Gn 1501–2100 IU) and 7.3% (309/4202) in group 3 (Gn>2100 IU). After adjusted for age, BMI, parity, blastocyst-stage ET and ovarian stimulation protocol, the logistic regression model also showed significant positive association between gonadotropin dosage and PTB (adjusted OR [aOR]=1.27 [95% CI: 1.04–1.54]). No significant association was found between the dosage of gonadotropins and the incidence of LBW: the incidence of LBW was 3.8% (208/4903) in group 1, 3.4% (145/3892) in group 2 and 3.6% (171/4202) in group 3. After adjusted for age, BMI and blastocyst-stage ET (yes vs no), the logistic regression model also showed that the dosage of gonadotropins was not associated with the risk of LBW (Table 3). Discussion Our study demonstrated that high gonadotropin dosage used for ovarian stimulation significantly positively associated with the risk of PTB in singletons born after fresh embryo transfer, even after adjusting for potential confounders. However, the dosage of exogenous gonadotropins was not associated with LBW, consistent with the previously study conducted by Griesinger et al.(Griesinger, Kolibianakis, Diedrich, & Ludwig, 2008). It has been speculated that gonadotropins used for ovarian stimulation might have detrimental effect on IVF outcomes. Previous study demonstrated that high gonadotropin dosage was associated with poor clinical pregnancy rate in normal-responder patients undergoing ART with long protocol(Yilmaz et al., 2013). Baker et.al revealed that gonadotropin dose was negatively associated with live birth rate (Baker, Brown, Luke, Smith, & Ireland, 2015). However, Barash et al. reported that high gonadotropin dosage didn’t affect blastocyst aneuploidy(Barash, Hinckley, Rosenbluth, Ivani, & Weckstein, 2017). Our study found that high gonadotropin dosage increased the risk of adverse perinatal outcome of PTB in singletons born after fresh embryo transfer, adding evidence of the potential adverse impact of high gonadotropin doses on IVF outcomes. Exogenous gonadotropins used for ovarian stimulation induce the development of multiple follicles and result in a supraphysiological endocrine level(Santos, Kuijk, & Macklon, 2009). The nonphysiological hormonal environment resulting from gonadotropin stimulation appeared to have a detrimental effect on perinatal outcomes by interfering trophoblast expansion and invasion(M. A. Mainigi et al., 2014). Pereira et al. illustrated that supraphysiologic estradiol (E 2 ) on the day of hCG trigger was an independent predictor for LBW in full-term singletons born after fresh embryo transfer (Pereira et al., 2017). Frozen embryo transfer (FET) provides more physiological uterine environment and improved perinatal outcomes when compared with fresh embryo transfer (Barnhart, 2014; Ishihara et al., 2014; Maheshwari, Kalampokas, Davidson, & Bhattacharya, 2013). However, the increased risk of perinatal complication was persistent in FET cycles despite the effect of stimulation was removed (Munch, Sparks, Zimmerman, Van Voorhis, & Duran, 2017; Pandey et al., 2012). Studies in the mouse have shown that superovulation with gonadotropins altered the expression of imprinted genes in oocytes, early embryos or midgestation placenta(Fortier, Lopes, Darricarrere, Martel, & Trasler, 2008; Ozturk, Yaba-Ucar, Sozen, Mutlu, & Demir, 2016). It is important to note that the perturbation of genomic imprinting was dose-dependent response to ovarian stimulation, and both mouse and human have epigenetic changes due to superovulation (Market-Velker, Zhang, Magri, Bonvissuto, & Mann, 2010; Sato, Otsu, Negishi, Utsunomiya, & Arima, 2007). Imprinted genes play important roles in the growth and development of embryo. Whether the altered expression of imprint genes during superovulation is related with preterm birth remains unknown, and possible mechanisms are still needed to explore in the future studies. A large cohort study from the UK including 65 868 singleton live birth outcomes revealed that a high number of oocytes retrieved (＞20 oocytes) was associated with a higher risk of PTB and LBW(Sunkara, La Marca, Seed, & Khalaf, 2015). Previous study found that ovarian hyperstimulation syndrome (OHSS) (often with a higher number of oocytes retrieved compared with non-OHSS pregnancies) was associated with PTB or LBW(Choux et al., 2017). But recent research suggested that the number of oocytes retrieved, even >20 oocytes, was not significantly associated with the risk of PTB, very PTB, small for gestational age, major birth defects and peri/neonatal death(Magnusson et al., 2018). Our study also showed that there was no association between the number of oocytes retrieved and the incidence of PTB and LBW. The association between the dosage of gonadotropins and PTB remains significant after adjusting for oocytes retrieved. Recent studies suggest that using high gonadotropin dosage does not necessarily improve the final outcome of IVF (Nargund, Datta, & Fauser, 2017; Sterrenburg et al., 2011). Milder ovarian stimulation protocols, in which a lower-than-average dosage of exogenous gonadotropins is given, might be a better choice (Revelli, Casano, Salvagno, & Delle Piane, 2011; Verberg et al., 2009). Further researches are needed to determine whether women using milder ovarian stimulation protocols have better perinatal outcomes. This study is a retrospective cohort study, and the population between different groups was heterogeneous. We have adjusted possible confounders in the adjusted logistic regression model. But residual confounding could not be avoided. Prospective randomized controlled studies are required to validate the association between gonadotropin dosage and perinatal outcomes. In conclusion, we found that the increased risk of PTB in singleton pregnancies in women receiving IVF/ICSI treatment could be partial attributed to the high dose of gonadotropins. Whether milder ovarian stimulation protocols using lower dose of gonadotropin is a better choice to avoid the risk of adverse outcomes is needed to verify in the future. Declarations Acknowledgments The authors would like to thank Jingfu Yang for his invaluable help during data collection. This study was funded by National Key Research and Development Program of China (2021YFC2700604), General Program of National Natural Science Foundation of China (82171648), Taishan Scholars Program for Young Experts of Shandong Province (tsqn201812154). Funding This study was funded by National Key Research and Development Program of China (2021YFC2700604), General Program of National Natural Science Foundation of China (82171648), Taishan Scholars Program for Young Experts of Shandong Province (tsqn201812154). Ethics approval and consent to participate: The study was approved by the Institutional Review Board of Center for Reproductive Medicine, Shandong University. 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Live birth and perinatal outcomes following stimulated and unstimulated IVF: analysis of over two decades of a nationwide data. Hum Reprod, 31 (10), 2261-2267. doi:10.1093/humrep/dew184 Verberg, M. F., Macklon, N. S., Nargund, G., Frydman, R., Devroey, P., Broekmans, F. J., & Fauser, B. C. (2009). Mild ovarian stimulation for IVF. Hum Reprod Update, 15 (1), 13-29. doi:10.1093/humupd/dmn056 Wang, Y. A., Sullivan, E. A., Black, D., Dean, J., Bryant, J., & Chapman, M. (2005). Preterm birth and low birth weight after assisted reproductive technology-related pregnancy in Australia between 1996 and 2000. Fertil Steril, 83 (6), 1650-1658. doi:10.1016/j.fertnstert.2004.12.033 Williams, M. A., Goldman, M. B., Mittendorf, R., & Monson, R. R. (1991). Subfertility and the risk of low birth weight. Fertil Steril, 56 (4), 668-671. Yilmaz, N., Yilmaz, S., Inal, H., Gorkem, U., Seckin, B., Turkkani, A., & Gulerman, C. (2013). Is there a detrimental effect of higher gonadotrophin dose on clinical pregnancy rate in normo-responders undergoing ART with long protocol? Arch Gynecol Obstet, 287 (5), 1039-1044. doi:10.1007/s00404-012-2673-z Tables Table 1. Baseline characteristics, ovarian stimulation parameters and perinatal outcomes of participants. Gonadotropin dosage per cycle ≤1500 IU 1501–2100 IU >2100 IU P-value Baseline characteristics No. 4903 3892 4202 Age (years) <0.001 <30 2447 (55.1) 1510 (42.1) 1306 (33.8) 30–34 1334 (30.0) 1236 (34.5) 1377 (35.7) 35–39 588 (25.5) 729 (20.3) 985 (25.5) ≥40 75 (19.8) 113 (3.2) 191 (5.0) BMI (kg/m 2 ) <0.001 <18.5 340 (6.9) 164 (4.2) 116 (2.8) 18.5–23.9 3174 (64.7) 2058 (52.9) 1781 (42.4) 24.0–27.9 1132 (23.1) 1215 (31.2) 1377 (32.8) ≥28 257 (5.2) 455 (11.7) 928 (22.1) Parity ≥1 923 (19.7) 920 (24.6) 1216 (30.0) <0.001 Prior preterm birth 7 (0.1) 10 (0.3) 10 (0.2) 0.44 Blastocyst-stage ET 1095 (22.3) 844 (21.7) 957 (22.8) 0.50 Insemination method (IVF) 3633 (74.1) 2919 (75.0) 3286 (78.2) <0.001 Ovarian stimulation parameters Dosage of gonadotropins (IU) 1235.5±211.2 1817.2±169.0 3033.6±893.1 Dosage of HCG (IU) 7384.5±1526.1 7737.9±1516.3 7990.2±1485.4 No. oocytes retrieved per cycle 20 136 (3.2) 101 (3.0) 96 (2.7) E2 level on the day of HCG trigger (pg/ml) 3185.2±1571 2966.0±1516.0 2781.9±1439.6 <0.001 Ovarian stimulation protocol <0.001 long GnRH agonist 2851 (58.2) 2367 (60.8) 2387 (56.8) short GnRH agonist 925 (18.9) 779 (20.0) 1013 (24.1) antagonist 1042 (21.3) 652 (16.8) 541 (12.9) Others 85 (1.7) 94 (2.4) 261 (6.2) Perinatal outcomes Mode of delivery (cesarean) 2939 (60.0) 2543 (65.3) 2933 (69.8) <0.001 Infant gender (male) 2552 (52.1) 2013 (51.7) 2133 (50.8) 0.45 Preterm delivery (<37 weeks) 255 (5.2) 232 (6.0) 309 (7.4) <0.001 Low birthweight (<2500 g) 208 (4.2) 145 (3.7) 171 (4.1) 0.47 Date: mean ± SD or (%) (no. /total no.). Table 2. Multiple logistic regression analysis of the association between the confounding variables, gonadotropins dosage and preterm birth (2100 309 (7.4) 1.45 (1.22, 1.72) 1.27 (1.04, 1.54) Female age (years) 39 30 (7.9) 1.41 (0.95, 2.08) 1.20 (0.78, 1.84) BMI (kg/m 2 ) <18.5 27 (4.4) 0.81 (0.54, 1.21) 0.78 (0.49, 1.23) 18.5–23.9 375 (5.4) Ref Ref 24.0–27.9 236 (6.3) 1.20 (1.01, 1.42) 1.17 (0.98, 1.40) ≥28 158 (9.6) 1.89 (1.55, 2.29) 1.71 (1.37, 2.12) Parity 0 544 (5.8) Ref Ref ≥1 211 (6.9) 1.21 (1.03, 1.43) 0.93 (0.76, 1.14) Insemination method (IVF vs ICSI) IVF 617 (6.3) Ref - ICSI 179 (5.7) 0.90 (0.76, 1.07) - Number of oocytes retrieved 1–4 109 (7.2) Ref - 5–9 238 (6.0) 0.82 (0.65, 1.04) - 10–15 208 (5.9) 0.81 (0.64, 1.03) - 16–20 116 (6.6) 0.92 (0.70, 1.20) - >20 19 (5.7) 0.78 (0.47, 1.30) - E2 level on the day of HCG trigger <3000 pg/ml 487 (6.4) Ref - ≥3000 pg/ml 309 (5.8) 0.90 (0.78, 1.04) - Blastocyst–stage ET No 589 (5.8) Ref Ref Yes 207 (7.2) 1.24 (1.06, 1.47) 1.24 (1.03, 1.49) Ovarian stimulation protocol Long GnRH agonist 449 (5.9) Ref Ref Short GnRH agonist 184 (6.8) 1.16 (0.97, 1.38) 1.13 (0.93, 1.37) Antagonist 123 (5.5) 0.93 (0.76, 1.14) 0.90 (0.71, 1.12) Others 40 (9.1) 1.60 (1.14, 2.24) 1.37 (0.94, 1.99) PTB: preterm birth; OR: odds ratio; 95% CI: 95% confidence interval for the odds ratio. a Adjusted for female age, BMI, parity, blastocyst-stage ET, ovarian stimulation protocol. Table 3. Multiple logistic regression analysis of the association between the confounding variables, gonadotropins dosage and low birthweight (<2500 g). LBW rate N (%) Unadjusted OR (95% CI) Adjusted a OR (95% CI) Gonadotropins dosage (IU) 2100 171 (4.1) 0.96 (0.78, 1.18) 0.98 (0.78, 1.23) Female age (years) 39 23 (6.1) 1.59 (1.02, 2.49) 1.67 (1.07, 2.62) BMI (kg/m 2 ) <18.5 35 (5.7) 1.37 (0.96, 1.97) 1.45 (0.98, 2.13) 18.5–23.9 293 (4.2) Ref Ref 24.0–27.9 127 (3.4) 0.81 (0.66, 1.00) 0.82 (0.66, 1.03) ≥28 69 (4.2) 1.01 (0.77, 1.32) 1.02 (0.77, 1.36) Parity 0 370 (3.9) Ref - ≥1 130 (4.3) 1.09 (0.89, 1.33) - Insemination method (IVF vs ICSI) IVF 410 (4.2) Ref - ICSI 114 (3.6) 0.86 (0.70, 1.06) - Number of oocytes retrieved 1–4 70 (4.6) Ref - 5–9 141 (3.5) 0.76 (0.57, 1.01) - 10–15 141 (4.0) 0.86 (0.64, 1.15） - 16–20 82 (4.7) 1.02 (0.73, 1.41) - >20 11 (3.3) 0.71 (0.37, 1.35) - E2 level on the day of HCG trigger <3000 pg/ml 289 (3.8) Ref - ≥3000 pg/ml 235 (4.4) 1.17 (0.98, 1.39) - Blastocyst–stage ET No 386 (3.8) Ref Ref Yes 138 (4.8) 1.26 (1.03, 1.54) 1.26 (1.02, 1.55) Ovarian stimulation protocol Long GnRH agonist 293 (3.9) Ref - Short GnRH agonist 116 (4.3) 1.11 (0.89, 1.39) - Antagonist 91 (4.1) 1.06 (0.83, 1.35) - Others 24 (5.5) 1.44 (0.94, 2.21) - LBW: low birthweight; OR: odds ratio; 95% CI: 95% confidence interval for the odds ratio. a Adjusted for female age, BMI, parity, blastocyst-stage ET, ovarian stimulation protocol. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2669191","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":188320810,"identity":"0ccc3317-df20-4d7f-8410-cae12818299b","order_by":0,"name":"Wei Zhou MD","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Zhou","suffix":"MD"},{"id":188320811,"identity":"d735cee1-c2a6-4937-999a-107e801937e8","order_by":1,"name":"Qianqian Wu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qianqian","middleName":"","lastName":"Wu","suffix":""},{"id":188320812,"identity":"9419776b-fe05-42b7-a635-6753a7e3a09c","order_by":2,"name":"Zhiyi Song","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhiyi","middleName":"","lastName":"Song","suffix":""},{"id":188320813,"identity":"ba2d9457-b529-4e34-ba23-93c5a87eb8a3","order_by":3,"name":"Jiahui Wang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jiahui","middleName":"","lastName":"Wang","suffix":""},{"id":188320814,"identity":"25b94f75-d238-4b5c-a273-cd5e4c0a4587","order_by":4,"name":"Zijiang Chen Chen","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zijiang","middleName":"Chen","lastName":"Chen","suffix":""},{"id":188320815,"identity":"875bc561-93b9-4768-9205-708bec232ce4","order_by":5,"name":"Junhao Yan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAArklEQVRIiWNgGAWjYHAC5gcJFTY8/OwNxGthM/hwJk1GsucACdZIzmw5bGNww4FI5QY3cgyMeRvO8zDcYGD88DGHSC2PeXfc5mGc3cAsOXMb0bacuc3DLHOAjZmXWC3SvG3neNgkEkjQIjmz7QAPD9FaJM88KwMGcjKPBM/BZuL8wnc8eTMwKu3s7Y83H/zwkRgtChcyDKBMxgYi1AOBfP/xB8SpHAWjYBSMgpELAIyuOopYRhK6AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-7110-8698","institution":"Provincial Hospital affiliated to Shandong University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Junhao","middleName":"","lastName":"Yan","suffix":""}],"badges":[],"createdAt":"2023-03-08 11:09:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2669191/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2669191/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":38929496,"identity":"b351f0e9-8a14-45ee-aaec-643e2b972254","added_by":"auto","created_at":"2023-06-22 13:44:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":382595,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2669191/v1/3b6b164b-3b06-477a-96cf-63d2cb6f882e.pdf"}],"financialInterests":"","formattedTitle":"High dosage of gonadotropins is associated with increased risk of preterm birth in singletons born after fresh embryo transfer","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePregnancies resulting from assisted reproductive technology (ART) are associated with a higher risk of adverse perinatal outcomes such as preterm birth (PTB) and low birth weight (LBW) compared with spontaneous pregnancies. The risk is present both in multiple and singleton pregnancies\u0026nbsp;(McDonald et al., 2009; Pandey, Shetty, Hamilton, Bhattacharya, \u0026amp; Maheshwari, 2012; Pastore \u0026amp; Williams, 2004). However, the reason of increased risk of adverse perinatal outcomes in singleton pregnancies is still not fully understood.\u003c/p\u003e\n\u003cp\u003eThe reasons of increased risk of adverse perinatal outcomes in singletons born after IVF/ICSI were multifactorial\u0026nbsp;(McGovern, Llorens, Skurnick, Weiss, \u0026amp; Goldsmith, 2004; Schieve et al., 2002). Previous study indicated that the underlying infertility itself seemed to have a negative impact on perinatal outcomes\u0026nbsp;(Williams, Goldman, Mittendorf, \u0026amp; Monson, 1991). Also, iatrogenic risks of adverse outcomes may come from the in vitro fertilization (IVF) laboratory procedures such as culture time and media composition, freezing/thawing techniques and specific laboratory procedures\u0026nbsp;(Alviggi et al., 2018; Pelkonen et al., 2010; Wang et al., 2005). Moreover, the ovarian stimulation with exogenous gonadotropins may also play a critical role in perinatal outcomes\u0026nbsp;(Klemetti, Sev\u0026oacute;n, Gissler, \u0026amp; Hemminki, 2010; Pinborg et al., 2013).\u003c/p\u003e\n\u003cp\u003eSuperovulation with exogenous gonadotropins is a necessary procedure in ART\u0026nbsp;(Homburg \u0026amp; Insler, 2002; Hughes, 2003). Administration of gonadotropins during ART affects the hormonal milieu at the time of follicular growth and embryos transfer, which may have detrimental effects on embryo development and perinatal outcomes\u0026nbsp;(Evans, Hannan, Hincks, Rombauts, \u0026amp; Salamonsen, 2012; Kelley et al., 2006; M. Mainigi et al., 2016; Santos, Kuijk, \u0026amp; Macklon, 2010; Verberg et al., 2009). More and more study indicated that the ovarian stimulation may be an important factor for adverse perinatal outcomes. Previous studies suggested that stimulated IVF was associated with a higher risk of adverse perinatal outcomes as compared with natural cycle IVF(Kamath, Kirubakaran, Mascarenhas, \u0026amp; Sunkara, 2018; Mak et al., 2016). However, a large dataset showed that there was no significant difference in the risk of PTB and LBW between stimulated and unstimulated IVF\u0026nbsp;(Sunkara, LaMarca, Polyzos, Seed, \u0026amp; Khalaf, 2016).\u003c/p\u003e\n\u003cp\u003ePossible influencing factors of adverse outcomes in ART singletons need to be further explored. Studies focusing on the association between the dosage of exogenous gonadotropins used for ovarian stimulation and perinatal outcomes were rare. The aim of this study was to explore the relationship between gonadotropins dosage and the perinatal outcomes of PTB and LBW in singletons born after fresh embryo transfer.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnonymous data were obtained from the Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University. This retrospective cohort study included 12997 singleton births from fresh IVF/ICSI cycles with either Day 3 or Day 5 embryo transfer (ET) between January 2013 and December 2020. Women undergoing their first IVF/ICSI cycles because of tubal factors, male factors, ovulatory disorder or others were included. All included women experienced a singleton birth after fresh embryo transfer. Women who had uterine malformations, smoking, using nature cycles in controlled ovarian hyperstimulation (COH), using donor oocytes, conceived multiple pregnancies or vanishing twins were excluded. This study was approved by the ethics committees of Reproductive Medicine Center of Shandong University.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy procedures and outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe exogenous gonadotropins used for ovarian stimulation included recombinant follicle-stimulating hormone (Puregon, MSD, USA; Gonal-f, Merck Serono, Germany; Urofollitropin for Injection, Livzon Pharmaceutical Group Inc., China; or Recombinant Human Follitropin for Injection, Gensci, China) and urinary human menopausal gonadotropin (Menotrophins for Injection, Livzon Pharmaceutical Group Inc., China; or Menopur, Ferring, Switzerland). The dosage of gonadotropins was adjusted according to the ovarian response. Urinary human chorionic gonadotropin (HCG) at a dose of 4000 to 10,000 IU was used to trigger oocyte maturation when follicles measured 18mm or more. Oocyte retrieval was performed 36 h after the trigger.\u003c/p\u003e\n\u003cp\u003eDay 3 embryos scoring was conducted by the morphologic criteria of Puissant et al.(Puissant, Van Rysselberge, Barlow, Deweze, \u0026amp; Leroy, 1987). And Day 5 embryos were scored according to Gardner morphologic criteria(Gardner, Lane, Stevens, Schlenker, \u0026amp; Schoolcraft, 2000). Luteal-phase support with Duphaston (Abbott, USA) and either Crinone (Merck Serono, Germany) or Utrogestan (Besins Manufacturing Belgium)\u0026nbsp;was initiated immediately after oocyte retrieval and was continued until\u0026nbsp;10 weeks of gestation.\u003c/p\u003e\n\u003cp\u003eLive-birth was defined as delivery of a viable neonate at 28 weeks or more of gestation. Occurrence of a live-birth at \u0026lt;37 weeks of gestation was defined as PTB. Birthweight \u0026lt;2500 grams was defined as LBW.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGonadotropin dosages were categorized into three groups according to tertile \u0026nbsp;(Group 1: \u0026le;1500 IU, Group 2: 1501\u0026ndash;2100 IU, and Group 3: \u0026gt;2100 IU). Inter-group difference of baseline characteristics was compared using Wilcoxon rank-sum test for non-normally distributed continuous variables and Chi-squared analysis for categorical variables. Adjusted logistic regression models were performed to evaluate the relationship between the exogenous gonadotropins dose and the risks of PTB and LBW. Based on our univariate analysis, the following variables differed within three Gonadotropin groups and also significantly associated with the risk of PTB or LBW were considered as potential confounders: maternal age, body mass index (BMI), parity, stage of embryo transferred and ovarian stimulation protocol. P-value of \u0026lt;0.05 was considered statistically significant. Analyses were performed using SAS software (version 9.4; SAS Institute, Cary, NC, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 12997 patients had singleton live-births after their first fresh IVF/ICSI embryo transfer (ET) cycle.\u0026nbsp;Clinical characteristics, cycle\u0026nbsp;parameters and perinatal outcomes are presented in Table I. The mean gonadotropin dosage\u0026nbsp;was 1991.0\u0026plusmn;926.9 IU.\u0026nbsp;Women using higher gonadotropin dosage were older and had a higher BMI level.\u0026nbsp;The overall incidence of PTB and LBW were 6.1% (796/12997) and 4.0% (524/12997), respectively.\u0026nbsp;The gestational week of PTB patients was 34.4\u0026plusmn;2.1 weeks. The mean birth weight for PTB infants was 2.0\u0026plusmn;0.4 kg.\u003c/p\u003e\n\u003cp\u003eTable 2 showed that gonadotropins dosage is positively associated with the incidence of PTB: 5.2% (255/4903) in group 1 (Gn\u0026le;1500 IU), 5.8% (232/3892) in group 2 (Gn 1501\u0026ndash;2100 IU) and 7.3% (309/4202) in group 3 (Gn\u0026gt;2100 IU). After adjusted\u0026nbsp;for\u0026nbsp;age, BMI, parity, blastocyst-stage ET and\u0026nbsp;ovarian stimulation protocol,\u0026nbsp;the logistic regression model also showed significant positive association between\u0026nbsp;gonadotropin dosage\u0026nbsp;and PTB\u0026nbsp;(adjusted OR [aOR]=1.27 [95% CI: 1.04\u0026ndash;1.54]).\u003c/p\u003e\n\u003cp\u003eNo significant association was found between the dosage of gonadotropins and the incidence of LBW: the incidence of LBW was 3.8% (208/4903) in group 1, 3.4% (145/3892) in group 2 and 3.6% (171/4202) in group 3. After adjusted for age, BMI and blastocyst-stage ET (yes vs no), the logistic regression model also showed that the dosage of gonadotropins was not associated with the risk of LBW (Table 3).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study demonstrated that high gonadotropin dosage used for ovarian stimulation significantly positively associated with the risk of PTB in singletons born after fresh embryo transfer,\u0026nbsp;even after adjusting for potential confounders. However, the dosage of exogenous gonadotropins was not associated with LBW,\u0026nbsp;consistent with the previously study conducted by\u0026nbsp;Griesinger et al.(Griesinger, Kolibianakis, Diedrich, \u0026amp; Ludwig, 2008).\u003c/p\u003e\n\u003cp\u003eIt has been speculated that gonadotropins used for ovarian stimulation might have detrimental effect on IVF outcomes. Previous study demonstrated that high gonadotropin dosage was associated with poor clinical pregnancy rate in normal-responder patients undergoing ART with long protocol(Yilmaz et al., 2013). Baker et.al revealed that gonadotropin dose was negatively associated with live birth rate (Baker, Brown, Luke, Smith, \u0026amp; Ireland, 2015). However, Barash et al. reported that high gonadotropin dosage didn\u0026rsquo;t affect blastocyst aneuploidy(Barash, Hinckley, Rosenbluth, Ivani, \u0026amp; Weckstein, 2017). Our study found that high gonadotropin dosage increased the risk of adverse perinatal outcome of PTB in singletons born after fresh embryo transfer, adding evidence of the potential adverse impact of high gonadotropin doses on IVF outcomes.\u003c/p\u003e\n\u003cp\u003eExogenous gonadotropins used for ovarian stimulation induce\u0026nbsp;the development of multiple follicles and result in a supraphysiological endocrine level(Santos, Kuijk, \u0026amp; Macklon, 2009). The nonphysiological hormonal environment resulting from gonadotropin stimulation appeared to have a detrimental effect on perinatal outcomes by interfering trophoblast expansion and invasion(M. A. Mainigi et al., 2014). Pereira et al. illustrated that supraphysiologic estradiol (E\u003csub\u003e2\u003c/sub\u003e) on the day of hCG trigger was an independent predictor for LBW in full-term singletons born after fresh embryo transfer\u0026nbsp;(Pereira et al., 2017). Frozen embryo transfer (FET) provides more physiological uterine environment and improved perinatal outcomes when compared with fresh embryo transfer\u0026nbsp;(Barnhart, 2014; Ishihara et al., 2014; Maheshwari, Kalampokas, Davidson, \u0026amp; Bhattacharya, 2013). However, the increased risk of perinatal complication was persistent in FET cycles despite the effect of stimulation was removed\u0026nbsp;(Munch, Sparks, Zimmerman, Van Voorhis, \u0026amp; Duran, 2017; Pandey et al., 2012).\u003c/p\u003e\n\u003cp\u003eStudies in the mouse have shown that superovulation with gonadotropins altered the expression of imprinted genes in oocytes, early embryos or midgestation placenta(Fortier, Lopes, Darricarrere, Martel, \u0026amp; Trasler, 2008; Ozturk, Yaba-Ucar, Sozen, Mutlu, \u0026amp; Demir, 2016). It is important to note that the perturbation of genomic imprinting was dose-dependent response to ovarian stimulation, and both mouse and human have epigenetic changes due to superovulation\u0026nbsp;(Market-Velker, Zhang, Magri, Bonvissuto, \u0026amp; Mann, 2010; Sato, Otsu, Negishi, Utsunomiya, \u0026amp; Arima, 2007). Imprinted genes play important roles in the growth and development of embryo. Whether the altered expression of imprint genes during superovulation is related with preterm birth remains unknown, and possible mechanisms are still needed to explore in the future studies.\u003c/p\u003e\n\u003cp\u003eA large cohort study from the UK including 65 868 singleton live birth outcomes revealed that a high number of oocytes retrieved (＞20 oocytes) was associated with a higher risk of PTB and LBW(Sunkara, La Marca, Seed, \u0026amp; Khalaf, 2015). Previous study found that ovarian hyperstimulation syndrome (OHSS) (often with a higher number of oocytes retrieved compared with non-OHSS pregnancies) was associated with PTB or LBW(Choux et al., 2017). But recent research suggested that the number of oocytes retrieved, even \u0026gt;20 oocytes, was not significantly associated with the risk of PTB, very PTB, small for gestational age, major birth defects and peri/neonatal death(Magnusson et al., 2018). Our study also showed that there was no association between the number of oocytes retrieved and the incidence of PTB and LBW. The association between the dosage of gonadotropins and PTB remains significant after adjusting for oocytes retrieved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRecent studies suggest that using high gonadotropin dosage does not necessarily improve the final outcome of IVF\u0026nbsp;(Nargund, Datta, \u0026amp; Fauser, 2017; Sterrenburg et al., 2011). Milder ovarian stimulation protocols, in which a lower-than-average dosage of exogenous gonadotropins is given, might be a better choice\u0026nbsp;(Revelli, Casano, Salvagno, \u0026amp; Delle Piane, 2011; Verberg et al., 2009).\u0026nbsp;Further researches are needed to determine whether women using milder ovarian stimulation protocols have better perinatal outcomes.\u003c/p\u003e\n\u003cp\u003eThis study is a retrospective cohort study, and the population between different groups was heterogeneous. We have adjusted possible confounders in the adjusted logistic regression model. But residual confounding could not be avoided.\u0026nbsp;Prospective randomized controlled studies are required to validate the association between\u0026nbsp;gonadotropin dosage and perinatal outcomes.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, we found that the increased risk of PTB in singleton pregnancies in women receiving IVF/ICSI treatment could be partial attributed to the high dose of gonadotropins. Whether milder ovarian stimulation protocols using lower dose of gonadotropin is a better choice to avoid the risk of adverse outcomes is needed to verify in the future.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Jingfu Yang for his invaluable help during data collection. This study was funded by National Key Research and Development Program of China (2021YFC2700604), General Program of National Natural Science Foundation of China (82171648), Taishan Scholars Program for Young Experts of Shandong Province (tsqn201812154).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by National Key Research and Development Program of China (2021YFC2700604), General Program of National Natural Science Foundation of China (82171648), Taishan Scholars Program for Young Experts of Shandong Province (tsqn201812154).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e The study was approved by the Institutional Review Board of Center for Reproductive Medicine, Shandong University. Informed consent was obtained from all individual participants included in the study.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflicts of interest in the study.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflict of interests，we do not have any possible conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAlviggi, C., Conforti, A., Carbone, I. F., Borrelli, R., de Placido, G., \u0026amp; Guerriero, S. (2018). Influence of cryopreservation on perinatal outcome after blastocyst- vs cleavage-stage embryo transfer: systematic review and meta-analysis. \u003cem\u003eUltrasound Obstet Gynecol, 51\u003c/em\u003e(1), 54-63. doi:10.1002/uog.18942\u003c/li\u003e\n \u003cli\u003eBaker, V. L., Brown, M. B., Luke, B., Smith, G. W., \u0026amp; Ireland, J. J. (2015). Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles. \u003cem\u003eFertil Steril, 104\u003c/em\u003e(5), 1145-1152 e1141-1145. doi:10.1016/j.fertnstert.2015.07.1151\u003c/li\u003e\n \u003cli\u003eBarash, O. O., Hinckley, M. D., Rosenbluth, E. M., Ivani, K. A., \u0026amp; Weckstein, L. N. (2017). High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer. \u003cem\u003eHum Reprod, 32\u003c/em\u003e(11), 2209-2217. doi:10.1093/humrep/dex299\u003c/li\u003e\n \u003cli\u003eBarnhart, K. T. (2014). 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Peri-Implantation Hormonal Milieu: Elucidating Mechanisms of Adverse Neurodevelopmental Outcomes. \u003cem\u003eReprod Sci, 23\u003c/em\u003e(6), 785-794. doi:10.1177/1933719115618280\u003c/li\u003e\n \u003cli\u003eMainigi, M. A., Olalere, D., Burd, I., Sapienza, C., Bartolomei, M., \u0026amp; Coutifaris, C. (2014). Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth. \u003cem\u003eBiol Reprod, 90\u003c/em\u003e(2), 26. doi:10.1095/biolreprod.113.110411\u003c/li\u003e\n \u003cli\u003eMak, W., Kondapalli, L. A., Celia, G., Gordon, J., DiMattina, M., \u0026amp; Payson, M. (2016). Natural cycle IVF reduces the risk of low birthweight infants compared with conventional stimulated IVF. \u003cem\u003eHum Reprod, 31\u003c/em\u003e(4), 789-794. doi:10.1093/humrep/dew024\u003c/li\u003e\n \u003cli\u003eMarket-Velker, B. A., Zhang, L., Magri, L. S., Bonvissuto, A. C., \u0026amp; Mann, M. R. (2010). 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Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis. \u003cem\u003eFertil Steril, 82\u003c/em\u003e(6), 1514-1520. doi:10.1016/j.fertnstert.2004.06.038\u003c/li\u003e\n \u003cli\u003eMunch, E. M., Sparks, A. E., Zimmerman, M. B., Van Voorhis, B. J., \u0026amp; Duran, E. H. (2017). High FSH dosing is associated with reduced live birth rate in fresh but not subsequent frozen embryo transfers. \u003cem\u003eHum Reprod, 32\u003c/em\u003e(7), 1402-1409. doi:10.1093/humrep/dex094\u003c/li\u003e\n \u003cli\u003eNargund, G., Datta, A. K., \u0026amp; Fauser, B. (2017). Mild stimulation for in vitro fertilization. \u003cem\u003eFertil Steril, 108\u003c/em\u003e(4), 558-567. doi:10.1016/j.fertnstert.2017.08.022\u003c/li\u003e\n \u003cli\u003eOzturk, S., Yaba-Ucar, A., Sozen, B., Mutlu, D., \u0026amp; Demir, N. (2016). 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M., Hyden-Granskog, C., . . . Hartikainen, A. L. (2010). Perinatal outcome of children born after frozen and fresh embryo transfer: the Finnish cohort study 1995-2006. \u003cem\u003eHum Reprod, 25\u003c/em\u003e(4), 914-923. doi:10.1093/humrep/dep477\u003c/li\u003e\n \u003cli\u003ePereira, N., Elias, R. T., Christos, P. J., Petrini, A. C., Hancock, K., Lekovich, J. P., \u0026amp; Rosenwaks, Z. (2017). Supraphysiologic estradiol is an independent predictor of low birth weight in full-term singletons born after fresh embryo transfer. \u003cem\u003eHum Reprod, 32\u003c/em\u003e(7), 1410-1417. doi:10.1093/humrep/dex095\u003c/li\u003e\n \u003cli\u003ePinborg, A., Wennerholm, U. B., Romundstad, L. B., Loft, A., Aittomaki, K., Soderstrom-Anttila, V., . . . Bergh, C. (2013). Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? 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The impact of ovarian stimulation for IVF on the developing embryo. \u003cem\u003eReproduction, 139\u003c/em\u003e(1), 23-34. doi:10.1530/rep-09-0187\u003c/li\u003e\n \u003cli\u003eSantos, M. A., Kuijk, E. W., \u0026amp; Macklon, N. S. (2010). The impact of ovarian stimulation for IVF on the developing embryo. \u003cem\u003eReproduction, 139\u003c/em\u003e(1), 23-34. doi:10.1530/REP-09-0187\u003c/li\u003e\n \u003cli\u003eSato, A., Otsu, E., Negishi, H., Utsunomiya, T., \u0026amp; Arima, T. (2007). Aberrant DNA methylation of imprinted loci in superovulated oocytes. \u003cem\u003eHum Reprod, 22\u003c/em\u003e(1), 26-35. doi:10.1093/humrep/del316\u003c/li\u003e\n \u003cli\u003eSchieve, L. A., Meikle, S. F., Ferre, C., Peterson, H. B., Jeng, G., \u0026amp; Wilcox, L. S. (2002). Low and very low birth weight in infants conceived with use of assisted reproductive technology. \u003cem\u003eN Engl J Med, 346\u003c/em\u003e(10), 731-737. doi:10.1056/NEJMoa010806\u003c/li\u003e\n \u003cli\u003eSterrenburg, M. D., Veltman-Verhulst, S. M., Eijkemans, M. J., Hughes, E. G., Macklon, N. S., Broekmans, F. J., \u0026amp; Fauser, B. C. (2011). Clinical outcomes in relation to the daily dose of recombinant follicle-stimulating hormone for ovarian stimulation in in vitro fertilization in presumed normal responders younger than 39 years: a meta-analysis. \u003cem\u003eHum Reprod Update, 17\u003c/em\u003e(2), 184-196. doi:10.1093/humupd/dmq041\u003c/li\u003e\n \u003cli\u003eSunkara, S. K., La Marca, A., Seed, P. T., \u0026amp; Khalaf, Y. (2015). Increased risk of preterm birth and low birthweight with very high number of oocytes following IVF: an analysis of 65 868 singleton live birth outcomes. \u003cem\u003eHum Reprod, 30\u003c/em\u003e(6), 1473-1480. doi:10.1093/humrep/dev076\u003c/li\u003e\n \u003cli\u003eSunkara, S. K., LaMarca, A., Polyzos, N. P., Seed, P. T., \u0026amp; Khalaf, Y. (2016). Live birth and perinatal outcomes following stimulated and unstimulated IVF: analysis of over two decades of a nationwide data. \u003cem\u003eHum Reprod, 31\u003c/em\u003e(10), 2261-2267. doi:10.1093/humrep/dew184\u003c/li\u003e\n \u003cli\u003eVerberg, M. F., Macklon, N. S., Nargund, G., Frydman, R., Devroey, P., Broekmans, F. J., \u0026amp; Fauser, B. C. (2009). Mild ovarian stimulation for IVF. \u003cem\u003eHum Reprod Update, 15\u003c/em\u003e(1), 13-29. doi:10.1093/humupd/dmn056\u003c/li\u003e\n \u003cli\u003eWang, Y. A., Sullivan, E. A., Black, D., Dean, J., Bryant, J., \u0026amp; Chapman, M. (2005). Preterm birth and low birth weight after assisted reproductive technology-related pregnancy in Australia between 1996 and 2000. \u003cem\u003eFertil Steril, 83\u003c/em\u003e(6), 1650-1658. doi:10.1016/j.fertnstert.2004.12.033\u003c/li\u003e\n \u003cli\u003eWilliams, M. A., Goldman, M. B., Mittendorf, R., \u0026amp; Monson, R. R. (1991). Subfertility and the risk of low birth weight. \u003cem\u003eFertil Steril, 56\u003c/em\u003e(4), 668-671.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eYilmaz, N., Yilmaz, S., Inal, H., Gorkem, U., Seckin, B., Turkkani, A., \u0026amp; Gulerman, C. (2013). Is there a detrimental effect of higher gonadotrophin dose on clinical pregnancy rate in normo-responders undergoing ART with long protocol? \u003cem\u003eArch Gynecol Obstet, 287\u003c/em\u003e(5), 1039-1044. doi:10.1007/s00404-012-2673-z\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Baseline characteristics, ovarian stimulation parameters and perinatal outcomes of participants.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"53.301320528211285%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGonadotropin dosage per cycle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"9.963985594237695%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0.4801920768307323%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026le;1500 IU\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u003cstrong\u003e1501\u0026ndash;2100 IU\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;2100 IU\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.963985594237695%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"0.4801920768307323%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eBaseline characteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eNo.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e4903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e3892\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e4202\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026lt;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2447 (55.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1510 (42.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1306 (33.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e30\u0026ndash;34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1334 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1236 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1377 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e35\u0026ndash;39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e588 (25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e729 (20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e985 (25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026ge;40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e75 (19.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e113 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e191 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eBMI\u0026nbsp;(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e340 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e164 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e116 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; 18.5\u0026ndash;23.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e3174 (64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2058 (52.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1781 (42.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; 24.0\u0026ndash;27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1132 (23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1215 (31.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1377 (32.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026ge;28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e257 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e455 (11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e928 (22.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eParity\u0026nbsp;\u0026ge;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e923 (19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e920 (24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1216 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Prior preterm birth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e7 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e10 (0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e10 (0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eBlastocyst-stage ET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1095 (22.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e844 (21.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e957 (22.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; Insemination method (IVF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e3633 (74.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2919 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e3286 (78.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eOvarian stimulation parameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eDosage of gonadotropins (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1235.5\u0026plusmn;211.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1817.2\u0026plusmn;169.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e3033.6\u0026plusmn;893.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eDosage of HCG (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e7384.5\u0026plusmn;1526.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e7737.9\u0026plusmn;1516.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e7990.2\u0026plusmn;1485.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eNo. oocytes retrieved per cycle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; 1\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e439 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e455 (13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e627 (17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; 5\u0026ndash;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1442 (34.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1187 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1361 (37.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; 10\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1445 (34.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1065 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1038 (28.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; 16\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e753 (17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e514 (15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e488 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026gt;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e136 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e101 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e96 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eE2\u003csup\u003e\u0026nbsp;\u003c/sup\u003elevel on the day of HCG trigger (pg/ml)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e3185.2\u0026plusmn;1571\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2966.0\u0026plusmn;1516.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2781.9\u0026plusmn;1439.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eOvarian stimulation protocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003elong GnRH agonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2851 (58.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2367 (60.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2387 (56.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eshort GnRH agonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e925 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e779 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1013 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eantagonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e1042 (21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e652 (16.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e541 (12.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e85 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e94 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e261 (6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003ePerinatal outcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mode of delivery (cesarean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2939 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2543 (65.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2933 (69.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eInfant gender (male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2552 (52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2013 (51.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e2133 (50.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003ePreterm delivery (\u0026lt;37 weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e255 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e232 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e309 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.25450180072029%\"\u003e\n \u003cp\u003eLow birthweight (\u0026lt;2500 g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e208 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e145 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.767106842737096%\"\u003e\n \u003cp\u003e171 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"10.444177671068427%\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eDate: mean \u0026plusmn; SD or (%) (no. /total no.).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Multiple logistic regression analysis of the association between the confounding variables, gonadotropins dosage and preterm birth (\u0026lt;37 weeks).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTB rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnadjusted OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted \u003csup\u003ea\u003c/sup\u003e OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eGonadotropins dosage (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026le;1500\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e255 (5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 1501\u0026ndash;2100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e232 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.16 (0.96, 1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.14 (0.93, 1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026gt;2100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e309 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.45 (1.22, 1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.27 (1.04, 1.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eFemale age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;30\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e303 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 30\u0026ndash;34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e208 (5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.91 (0.76, 1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.87 (0.72, 1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 35\u0026ndash;39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e184 (8.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.42 (1.18, 1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.29 (1.03, 1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026gt;39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e30 (7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.41 (0.95, 2.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.20 (0.78, 1.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e27 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.81 (0.54, 1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.78 (0.49, 1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e18.5\u0026ndash;23.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e375 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 24.0\u0026ndash;27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e236 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.20 (1.01, 1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.17 (0.98, 1.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026ge;28\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e158 (9.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.89 (1.55, 2.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.71 (1.37, 2.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eParity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e544 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026ge;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e211 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.21 (1.03, 1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.93 (0.76, 1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eInsemination method (IVF vs ICSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e617 (6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e179 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.90 (0.76, 1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eNumber of oocytes retrieved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 1\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e109 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 5\u0026ndash;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e238 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.82 (0.65, 1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 10\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e208 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.81 (0.64, 1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e16\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e116 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.92 (0.70, 1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e19 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.78 (0.47, 1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eE2 level on the day of HCG trigger\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;3000 pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e487 (6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026ge;3000 pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e309 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.90 (0.78, 1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eBlastocyst\u0026ndash;stage ET\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e589 (5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e207 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.24 (1.06, 1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.24 (1.03, 1.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eOvarian stimulation protocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; Long GnRH agonist\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e449 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; Short GnRH agonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e184 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.16 (0.97, 1.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.13 (0.93, 1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eAntagonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e123 (5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.93 (0.76, 1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.90 (0.71, 1.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; Others\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e40 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.60 (1.14, 2.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.37 (0.94, 1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePTB: preterm birth; OR: odds ratio; 95% CI: 95% confidence interval for the odds ratio.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eAdjusted for female age, BMI, parity, blastocyst-stage ET, ovarian stimulation protocol.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Multiple logistic regression analysis of the association between the confounding variables, gonadotropins dosage and low birthweight (\u0026lt;2500 g).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLBW rate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eN (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnadjusted OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted \u003csup\u003ea\u003c/sup\u003e OR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eGonadotropins dosage (IU)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;1500\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e208 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 1500\u0026ndash;2100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e145 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.87 (0.70, 1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.92 (0.74, 1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026gt;2100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e171 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.96 (0.78, 1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.98 (0.78, 1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eFemale age (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;30\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e205 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 30\u0026ndash;34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e144 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.93 (0.75, 1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.95 (0.76, 1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 35\u0026ndash;39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e108 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.22 (0.96, 1.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.26 (0.99, 1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026gt;39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e23 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.59 (1.02, 2.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.67 (1.07, 2.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e35 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.37 (0.96, 1.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.45 (0.98, 2.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e18.5\u0026ndash;23.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e293 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 24.0\u0026ndash;27.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e127 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.81 (0.66, 1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e0.82 (0.66, 1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026ge;28\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e69 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.01 (0.77, 1.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.02 (0.77, 1.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eParity\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e370 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026ge;1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e130 (4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.09 (0.89, 1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eInsemination method (IVF vs ICSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eIVF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e410 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eICSI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e114 (3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.86 (0.70, 1.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eNumber of oocytes retrieved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 1\u0026ndash;4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e70 (4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 5\u0026ndash;9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e141 (3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.76 (0.57, 1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; 10\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e141 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;0.86 (0.64, 1.15）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e16\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e82 (4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.02 (0.73, 1.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp;\u0026gt;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e11 (3.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e0.71 (0.37, 1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eE2 level on the day of HCG trigger\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;3000 pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e289 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026ge;3000 pg/ml\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e235 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.17 (0.98, 1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eBlastocyst\u0026ndash;stage ET\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e386 (3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e138 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.26 (1.03, 1.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e1.26 (1.02, 1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eOvarian stimulation protocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Long GnRH agonist\u003csup\u003e\u0026nbsp;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e293 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003eRef\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; Short GnRH agonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e116 (4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.11 (0.89, 1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003eAntagonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e91 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.06 (0.83, 1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"30.502392344497608%\"\u003e\n \u003cp\u003e\u0026nbsp; Others\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.181818181818183%\"\u003e\n \u003cp\u003e24 (5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.086124401913874%\"\u003e\n \u003cp\u003e1.44 (0.94, 2.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.229665071770334%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLBW: low birthweight; OR: odds ratio; 95% CI: 95% confidence interval for the odds ratio.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003eAdjusted for female age, BMI, parity, blastocyst-stage ET, ovarian stimulation protocol.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"fresh embryo transfer, gonadotropin dosage, preterm birth, low birth weight, ovarian stimulation","lastPublishedDoi":"10.21203/rs.3.rs-2669191/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2669191/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eResearch Question:\u003c/strong\u003eDoes high gonadotropin dosage affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) in singletons born after fresh embryo transfer (ET) cycles?\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign: \u003c/strong\u003eThis retrospective cohort study included 12997 singleton births after fresh ET cycles in China from January2013 to December 2020. All women underwent their first IVF/ICSI cycle. Patients were categorized into three groups according to the tertile of total gonadotropin dosage (≤1500 IU, 1501–2100 IU, \u0026gt;2100 IU). Adjusted logistic regression models were performed to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between gonadotropin dosage and the incidence of PTB and LBW.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe incidence of PTB and LBW were 6.1% (796/12997) and 4.0% (524/12997), respectively. The incidence of PTB rose from 5.2% (Gn≤1500 IU) to 7.4% (Gn\u0026gt;2100 IU). Compared with the lowest dosage group (≤1500 IU), an elevated incidence of PTB was observed at the highest gonadotropin dosage group (\u0026gt;2100 IU) in adjusted logistic regression model (adjusted OR [aOR]=1.14 [95% CI: 1.04–1.54]). However, the risk of LBW was comparable in three groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eHigh gonadotropindosage was significantly associated with the increase of PTB risk in singletons born after fresh embryo transfer. Whether mild stimulation regimens using lower dose of gonadotropin could improve pregnancy outcomes needs to be verified in the future studies.\u003c/p\u003e","manuscriptTitle":"High dosage of gonadotropins is associated with increased risk of preterm birth in singletons born after fresh embryo transfer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-04-04 03:51:52","doi":"10.21203/rs.3.rs-2669191/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ebeac8ea-f186-431c-882d-6bef57ce392e","owner":[],"postedDate":"April 4th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-06-22T13:44:06+00:00","versionOfRecord":[],"versionCreatedAt":"2023-04-04 03:51:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2669191","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2669191","identity":"rs-2669191","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}