Abstract
Research question
What are the factors associated with the increased incidence of pre-eclampsia in pregnancies
conceived through IVF using autologous oocytes?
Design
A nested case–control study from the combined cohort of three multicentre randomized
trials comparing fresh to frozen embryo transfer, including women who achieved clinical
pregnancy after the first embryo transfer. Multivariable logistic regression was used
to assess the effect of baseline characteristics, ovarian response parameters, type
of fertilization, type of embryo transfer, and number of gestational sacs on the risk
of pre-eclampsia.
Results
There were 2965 clinical pregnancies and 90 women were diagnosed with pre-eclampsia.
Twin gestations (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.50–3.66), mean
arterial pressure (OR 1.04, 95% CI 1.01–1.07), frozen embryo transfer (OR 2.06, 95%
CI 1.27–3.35), body mass index (BMI) (OR 1.10, 95% CI 1.02–1.18), progesterone level
on the day of human chorionic gonadotrophin trigger (OR 1.53, 95% CI 1.07–2.20), and
the total dose of gonadotrophin (OR 0.999, 95% CI 0.999–1.000, P = 0.037) were associated with the risk of pre-eclampsia. When the analysis was confined
to women who underwent frozen embryo transfer, twin gestations (OR 2.44, 95% CI 1.43–4.18),
BMI (OR 1.13, 95% CI 1.03–1.23) and the total dose of gonadotrophin (OR 0.999, 95%
CI 0.999–1.000, P = 0.014) were still related to the risk of pre-eclampsia. The embryo stage at transfer
was not included in the final models.
Conclusions
Frozen embryo transfer was an independent risk factor of pre-eclampsia in assisted
reproductive technology. The high ovarian response may also increase the risk of pre-eclampsia.
The embryo stage at transfer was not related to the risk of pre-eclampsia.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Reproductive BioMedicine OnlineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics.Placenta. 2015; 36: 1455-1462
- Infertility service use in the United States: data from the National Survey of Family Growth, 1982–2010.Natl. Health Stat. Report. 2014; 22: 1-21
- Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome.N. Engl. J. Med. 2016; 375: 523-533
- Hyper response to ovarian stimulation affects the follicular fluid metabolomic profile of women undergoing IVF similarly to polycystic ovary syndrome.Metabolomics. 2018; 14: 51
- Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment.J. Assist. Reprod. Genet. 2015; 32: 45-54
- Outcomes of singleton births after blastocyst versus non blastocyst transfer in assisted reproductive technology.Fertil. Steril. 2012; 97: 579-584
- Neonatal and maternal outcome after frozen embryo transfer: increased risks in programmed cycles.Am. J. Obstet. Gynecol. 2019; S0002–9378: 30487-30489
- Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology.Cochrane Database Syst. Rev. 2012; 7CD002118
- The impact of donor insemination on the risk of preeclampsia: a systematic review and meta-analysis.Eur. J. Obstet. Gynecol. Reprod. Biol. 2014; 182: 160-166
- A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome.Hum. Reprod. Update. 2006; 12: 13-21
- Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies.BMJ. 2004; 328: 261
- Genome-wide microRNA expression profiling in placentae from frozen-thawed blastocyst transfer.Clin. Epigenetics. 2017; 9: 79
- Monitoring health outcomes of assisted reproductive technology.N. Engl. J. Med. 2014; 371: 91-93
- Is the use of donor sperm associated with a higher incidence of preeclampsia in women who achieve pregnancy after intrauterine insemination?.Fertil. Steril. 2010; 93: 1124-1127
- Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.N. Engl. J. Med. 2014; 371: 119-129
- Obstetrical and perinatal outcomes following blastocyst transfer compared with cleavage transfer: a systematic review and meta-analysis.Hum. Reprod. 2016; 31: 2561-2569
- Risk of hypertensive disorders in pregnancies following assisted reproductive technology: a cohort study from the CoNARTaS group.Hum. Reprod. 2015; 30: 1724-1731
- Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis.Hum. Reprod. Update. 2012; 18: 485-503
- In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos.N. Engl. J. Med. 2006; 354: 1139-1146
- Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines.Clin. J. Am. Soc. Nephrol. 2016; 11: 1102-1113
- Transfer of Fresh versus Frozen Embryos in Ovulatory Women.N. Engl. J. Med. 2018; 378: 126-136
- Embryo cryopreservation and preeclampsia risk.Fertil. Steril. 2017; 108: 784-790
- Impact of high serum progesterone during the late follicular phase on IVF outcome.Reprod. Biomed. Online. 2014; 29: 177-186
- The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP.Pregnancy Hypertens. 2014; 4: 97-104
- Increased Preeclampsia Risk and Reduced Aortic Compliance WithIn vitro Fertilization Cycles in the Absence of a Corpus Luteum.Hypertension. 2019; 73: 640-649
- Increased incidence of gestational hypertension and preeclampsia after assisted reproductive technology treatment.Fertil. Steril. 2016; 105: 920-926
- Embryo vitrification affects the methylation of the H19/Igf2 differentially methylated domain and the expression of H19 and Igf2.Fertil. Steril. 2010; 93: 2729-2733
- Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomized controlled trial.Lancet. 2019; 393: 1310-1318
- Maternal and Live-birth Outcomes of Pregnancies following Assisted Reproductive Technology: A Retrospective Cohort Study.Sci. Rep. 2016; 6: 35141
Biography

Key message
For women receiving assisted reproductive technology treatment, frozen embryo transfer was an independent risk factor of pre-eclampsia. The high ovarian response may also contribute to the risk of pre-eclampsia. The embryo stage at transfer was not related to the risk of pre-eclampsia. Further studies are needed to evaluate the underlying mechanism.
Article info
Publication history
Published online: September 17, 2019
Accepted:
September 11,
2019
Received in revised form:
August 13,
2019
Received:
June 5,
2019
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.