Skip to main content

Advertisement

Log in

Ovarian Hyperstimulation Syndrome Is Associated with a High Secondary Sex Ratio in Fresh IVF Cycles with Cleavage-Stage Embryo Transfer: Results for a Cohort Study

  • Reproductive Biology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

The sex ratio at birth is defined as the secondary sex ratio (SSR). Ovarian hyperstimulation syndrome (OHSS) is a serious and iatrogenic complication associated with controlled ovarian stimulation (COS) during assisted reproductive technology (ART) treatments. It has been hypothesized that the human SSR is partially controlled by parental hormone levels around the time of conception. Given the aberrant hormonal profiles observed in patients with OHSS, this retrospective study was designed to evaluate the impact of OHSS on the SSR. In this study, all included patients were divided into 3 groups: non-OHSS (n=2777), mild OHSS (n=644), and moderate OHSS (n=334). Our results showed that the overall SSR for the study population was 1.033. The SSR was significantly increased in patients with moderate OHSS (1.336) compared to non-OHSS patients (1.002) (p=0.048). Subgroup analyses showed that increases in the SSR in patients with moderate OHSS were observed in the IVF group (1.323 vs 1.052; p=0.043), but not in the ICSI groups (1.021 vs 0.866; p=0.732). In addition, the elevated serum estradiol (E2) and progesterone (P4) levels in OHSS patients were not associated with SSR. In this study, for the first time, we report that a high SSR is associated with OHSS in patients who received fresh IVF treatments. The increases in SSR in OHSS patients are not attributed to the high serum E2 and P4 levels. Our findings may make both ART clinicians and patients more aware of the influences of ART treatments on the SSR and allow clinicians to counsel patients more appropriately.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Pergament E, Toydemir PB, Fiddler M. Sex ratio: a biological perspective of ‘Sex and the City’. Reprod BioMed Online. 2002;5(1):43–6. https://doi.org/10.1016/s1472-6483(10)61596-9.

    Article  PubMed  Google Scholar 

  2. Chao F, Gerland P, Cook AR, Alkema L. Systematic assessment of the sex ratio at birth for all countries and estimation of national imbalances and regional reference levels. Proc Natl Acad Sci U S A. 2019;116(19):9303–11. https://doi.org/10.1073/pnas.1812593116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ein-Mor E, Mankuta D, Hochner-Celnikier D, Hurwitz A, Haimov-Kochman R. Sex ratio is remarkably constant. Fertil Steril. 2010;93(6):1961–5. https://doi.org/10.1016/j.fertnstert.2008.12.036.

    Article  PubMed  Google Scholar 

  4. Terrell ML, Hartnett KP, Marcus M. Can environmental or occupational hazards alter the sex ratio at birth? A systematic review Emerging health threats journal. Emerg Health Threats J. 2011;4:7109. https://doi.org/10.3402/ehtj.v4i0.7109.

  5. Seth S. Sex selective feticide in India. J Assist Reprod Genet. 2007;24(5):153–4. https://doi.org/10.1007/s10815-007-9109-x.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Macmahon B, Pugh TF. Sex ratio of white births in the United States during the Second World War. Am J Hum Genet. 1954;6(2):284–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Rueness J, Vatten L, Eskild A. The human sex ratio: effects of maternal age. Hum Reprod. 2012;27(1):283–7. https://doi.org/10.1093/humrep/der347.

    Article  PubMed  Google Scholar 

  8. Kallen B, Finnstrom O, Nygren KG, Olausson PO. In vitro fertilization (IVF) in Sweden: infant outcome after different IVF fertilization methods. Fertil Steril. 2005;84(3):611–7. https://doi.org/10.1016/j.fertnstert.2005.02.038.

    Article  PubMed  Google Scholar 

  9. Thatcher SS, Restrepo U, Lavy G, DeCherney AH. In-vitro fertilisation and sex ratio. Lancet. 1989;1(8645):1025–6. https://doi.org/10.1016/s0140-6736(89)92674-3.

    Article  CAS  PubMed  Google Scholar 

  10. Supramaniam PR, Mittal M, Ohuma EO, Lim LN, McVeigh E, Granne I, et al. Secondary sex ratio in assisted reproduction: an analysis of 1 376 454 treatment cycles performed in the UK. Human reproduction open. Hum Reprod Open. 2019;2019(4):hoz020. https://doi.org/10.1093/hropen/hoz020.

  11. Maalouf WE, Mincheva MN, Campbell BK, Hardy IC. Effects of assisted reproductive technologies on human sex ratio at birth. Fertil Steril. 2014;101(5):1321–5. https://doi.org/10.1016/j.fertnstert.2014.01.041.

    Article  PubMed  Google Scholar 

  12. Dean JH, Chapman MG, Sullivan EA. The effect on human sex ratio at birth by assisted reproductive technology (ART) procedures--an assessment of babies born following single embryo transfers, Australia and New Zealand, 2002-2006. BJOG : an international journal of obstetrics and gynaecology. BJOG. 2010;117(13):1628–34. https://doi.org/10.1111/j.1471-0528.2010.02731.x.

  13. Luna M, Duke M, Copperman A, Grunfeld L, Sandler B, Barritt J. Blastocyst embryo transfer is associated with a sex-ratio imbalance in favor of male offspring. Fertil Steril. 2007;87(3):519–23. https://doi.org/10.1016/j.fertnstert.2006.06.058.

    Article  PubMed  Google Scholar 

  14. Menezo YJ, Chouteau J, Torello J, Girard A, Veiga A. Birth weight and sex ratio after transfer at the blastocyst stage in humans. Fertil Steril. 1999;72(2):221–4. https://doi.org/10.1016/s0015-0282(99)00256-3.

    Article  CAS  PubMed  Google Scholar 

  15. James WH. Evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels at the time of conception. J Theor Biol. 1996;180(4):271–86. https://doi.org/10.1006/jtbi.1996.0102.

    Article  CAS  PubMed  Google Scholar 

  16. James WH. Further evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. Hum Reprod. 2004;19(6):1250–6. https://doi.org/10.1093/humrep/deh245.

    Article  CAS  PubMed  Google Scholar 

  17. Zivi E, Simon A, Laufer N. Ovarian hyperstimulation syndrome: definition, incidence, and classification. Semin Reprod Med. 2010;28(6):441–7. https://doi.org/10.1055/s-0030-1265669.

    Article  CAS  PubMed  Google Scholar 

  18. Nastri CO, Teixeira DM, Moroni RM, Leitao VM, Martins WP. Ovarian hyperstimulation syndrome: pathophysiology, staging, prediction and prevention. Ultrasound Obstet Gynecol. 2015;45(4):377–93. https://doi.org/10.1002/uog.14684.

    Article  CAS  PubMed  Google Scholar 

  19. Lee TH, Liu CH, Huang CC, Wu YL, Shih YT, Ho HN, et al. Serum anti-Mullerian hormone and estradiol levels as predictors of ovarian hyperstimulation syndrome in assisted reproduction technology cycles. Hum Reprod. 2008;23(1):160–7. https://doi.org/10.1093/humrep/dem254.

  20. Hendriks DJ, Klinkert ER, Bancsi LF, Looman CW, Habbema JD, te Velde ER, et al. Use of stimulated serum estradiol measurements for the prediction of hyperresponse to ovarian stimulation in in vitro fertilization (IVF). J Assist Reprod Genet. 2004;21(3):65–72. https://doi.org/10.1023/b:jarg.0000027016.65749.ad.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Practice Committee of the American Society for Reproductive Medicine. Electronic address Aao, Practice Committee of the American Society for Reproductive M. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fertil Steril 2016;106(7):1634-1647. doi:https://doi.org/10.1016/j.fertnstert.2016.08.048.

  22. Obel C, Henriksen TB, Secher NJ, Eskenazi B, Hedegaard M. Psychological distress during early gestation and offspring sex ratio. Hum Reprod. 2007;22(11):3009–12. https://doi.org/10.1093/humrep/dem274.

    Article  PubMed  Google Scholar 

  23. Norberg K. Partnership status and the human sex ratio at birth. Proc Biol Sci. 2004;271(1555):2403–10. https://doi.org/10.1098/rspb.2004.2857.

    Article  PubMed  PubMed Central  Google Scholar 

  24. James WH. The variations of human sex ratio at birth during and after wars, and their potential explanations. J Theor Biol. 2009;257(1):116–23. https://doi.org/10.1016/j.jtbi.2008.09.028.

    Article  PubMed  Google Scholar 

  25. Fukuda M, Fukuda K, Shimizu T, Moller H. Decline in sex ratio at birth after Kobe earthquake. Hum Reprod. 1998;13(8):2321–2. https://doi.org/10.1093/humrep/13.8.2321.

    Article  CAS  PubMed  Google Scholar 

  26. Kasum M, Oreskovic S, Jezek D. Spontaneous ovarian hyperstimulation syndrome. Coll Antropol. 2013;37(2):653–6.

    PubMed  Google Scholar 

  27. Aboulghar M. Prediction of ovarian hyperstimulation syndrome (OHSS). Estradiol level has an important role in the prediction of OHSS. Hum Reprod. 2003;18(6):1140–1. https://doi.org/10.1093/humrep/deg208.

    Article  CAS  PubMed  Google Scholar 

  28. Yuen BH, McComb P, Sy L, Lewis J, Cannon W. Plasma prolactin, human chorionic gonadotropin, estradiol, testosterone, and progesterone in the ovarian hyperstimulation syndrome. Am J Obstet Gynecol. 1979;133(3):316–20. https://doi.org/10.1016/0002-9378(79)90686-0.

    Article  CAS  PubMed  Google Scholar 

  29. Ujioka T, Matsuura K, Kawano T, Okamura H. Role of progesterone in capillary permeability in hyperstimulated rats. Hum Reprod. 1997;12(8):1629–34. https://doi.org/10.1093/humrep/12.8.1629.

    Article  CAS  PubMed  Google Scholar 

  30. Lee FK, Lai TH, Lin TK, Horng SG, Chen SC. Relationship of progesterone/estradiol ratio on day of hCG administration and pregnancy outcomes in high responders undergoing in vitro fertilization. Fertil Steril. 2009;92(4):1284–9. https://doi.org/10.1016/j.fertnstert.2008.08.024.

    Article  CAS  PubMed  Google Scholar 

  31. Perret M. Relationship between urinary estrogen levels before conception and sex ratio at birth in a primate, the gray mouse lemur. Hum Reprod. 2005;20(6):1504–10. https://doi.org/10.1093/humrep/deh802.

    Article  CAS  PubMed  Google Scholar 

  32. de Ziegler D, Fanchin R, de Moustier B, Bulletti C. The hormonal control of endometrial receptivity: estrogen (E2) and progesterone. J Reprod Immunol. 1998;39(1-2):149–66. https://doi.org/10.1016/s0165-0378(98)00019-9.

    Article  PubMed  Google Scholar 

  33. Xiong F, Sun Q, Li GG, Chen PL, Yao ZH, Wan CY, et al. Initial serum HCG levels are higher in pregnant women with a male fetus after fresh or frozen single blastocyst transfer: a retrospective cohort study. Taiwan J Obstet Gynecol. 2019;58(6):833–9. https://doi.org/10.1016/j.tjog.2019.09.019.

  34. Fang L, He J, Yan Y, Jia Q, Yu Y, Zhang R, et al. Blastocyst-stage embryos provide better frozen-thawed embryo transfer outcomes for young patients with previous fresh embryo transfer failure. Aging. 2020;12(8):6981–9. https://doi.org/10.18632/aging.103055.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Zhu J, Zhuang X, Chen L, Liu P, Qiao J. Effect of embryo culture media on percentage of males at birth. Hum Reprod. 2015;30(5):1039–45. https://doi.org/10.1093/humrep/dev049.

    Article  CAS  PubMed  Google Scholar 

  36. Al-Jaroudi D, Salim G, Baradwan S. Neonate female to male ratio after assisted reproduction following antagonist and agonist protocols. Medicine. 2018;97(38):e12310. https://doi.org/10.1097/MD.0000000000012310.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Mills JL, England L, Granath F, Cnattingius S. Cigarette smoking and the male-female sex ratio. Fertil Steril. 2003;79(5):1243–5. https://doi.org/10.1016/s0015-0282(03)00156-0.

    Article  PubMed  Google Scholar 

  38. Rosenfeld CS, Roberts RM. Maternal diet and other factors affecting offspring sex ratio: a review. Biol Reprod. 2004;71(4):1063–70. https://doi.org/10.1095/biolreprod.104.030890.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors also thank the staff in the Center for Reproductive Medicine at the First Affiliated Hospital of Zhengzhou University for their assistance.

Funding

This work was supported by the operating grant from the National Natural Science Foundation of China (32070848), the Key R&D Program of Henan Province (202102310062), Henan Province Medical Science and Technique R&D Program (SBGJ202002052), and Special Fund for Young Teachers from the Zhengzhou University (JC202054006) to Lanlan Fang as well as by the Research Fund for International Young Scientists from the National Natural Science Foundation of China (32050410302) and Henan Province Medical Science and Technique R&D Program (SBGJ202002046) to Jung-Chien Cheng. This work was also supported by the National Natural Science Foundation of China for the International (Regional) Cooperation and Exchange Projects (81820108016) and the National Key R&D Program of China (2019YFA 0110900) to Ying-Pu Sun.

Author information

Authors and Affiliations

Authors

Contributions

LF and YPS contributed to the study design, analysis, and interpretation of data. LF, JCC, and YPS contributed to manuscript drafting and critical discussion. QJ, ZW, ZW, YY, and BL collected data, analyzed data, and prepared the figures.

Corresponding author

Correspondence to Lanlan Fang.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jia, Q., Fang, L., Wang, Z. et al. Ovarian Hyperstimulation Syndrome Is Associated with a High Secondary Sex Ratio in Fresh IVF Cycles with Cleavage-Stage Embryo Transfer: Results for a Cohort Study. Reprod. Sci. 28, 3341–3351 (2021). https://doi.org/10.1007/s43032-021-00637-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-021-00637-9

Keywords

Navigation