Increased risk of maternal and neonatal complications in hormone replacement therapy cycles in frozen embryo transfer

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Abstract

Background

The endometrial preparation during frozen embryo transfer (FET) can be performed by natural cycle (NC), hormone replacement therapy (HRT) cycle and cycle with ovulation induction (OI). Whether different FET preparation protocols can affect maternal and neonatal outcomes is still inconclusive.

Methods

This was a retrospective cohort study that included 6886 women who delivered singleton live birth babies after 28 weeks of pregnancy underwent FET from January, 2015 to July, 2018. Women were divided into three groups according to the protocols used for endometrial preparation during FET: NC group ( N = 4727), HRT group ( N = 1642) and OI group ( N = 517).

Results

After adjusting for the effect of age, body mass index (BMI), irregular menstruation, antral follicle count (AFC), endometrial thickness, the levels of testosterone, anti-Müllerian hormone (AMH), preconceptional fasting glucose (PFG), systolic and diastolic pressure et al., the HRT group had higher risk of hypertensive disorders of pregnancy (HDP) compared with the NC group (adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.54–2.60). Singletons born after HRT FET were at increased risk of low birth weight (LBW) compared to NC group (aOR 1.49, 95%CI 1.09–2.06). The risks of preterm birth (PTB) in the HRT and OI group were elevated compared with the NC group (aOR 1.78, 95%CI 1.39–2.28 and aOR 1.51, 95%CI 1.02–2.23, respectively).

Conclusions

The HRT protocol for endometrial preparation during frozen embryo transfer of blastocysts was associated with increased risk of maternal and neonatal complications, compared to the NC and OI protocol.

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Most cited references 33

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The uterine spiral arteries in human pregnancy: facts and controversies.

R Pijnenborg, L Vercruysse, M. Hanssens (2006)

Uterine spiral arteries play a vital role in supplying nutrients to the placenta and fetus, and for this purpose they are remodelled into highly dilated vessels by the action of invading trophoblast (physiological change). Knowledge of the mechanisms of these changes is relevant for a better understanding of pre-eclampsia and other pregnancy complications which show incomplete spiral artery remodelling. Controversies still abound concerning different steps in these physiological changes, and several of these disagreements are highlighted in this review, thereby suggesting directions for further research. First, a better definition of the degree of decidua- versus trophoblast-associated remodelling may help to devise a more adequate terminology. Other contestable issues are the vascular plugging and its relation with oxygen, trophoblast invasion from the outside or the inside of the vessels (intravasation versus extravasation), the impact of haemodynamics on endovascular migration, the replacement of arterial components by trophoblast, maternal tissue repair mechanisms and the role of uterine natural killer (NK) cells. Several of these features may be disturbed in complicated pregnancies, including the early decidua-associated vascular remodelling, vascular plugging and haemodynamics. The hyperinflammatory condition of pre-eclampsia may be responsible for vasculopathies such as acute atherosis, although the overall impact of such lesions on placental function is far from clear. Several features of the human placental bed are mirrored by processes in other species with haemochorial placentation, and studying such models may help to illuminate poorly understood aspects of human placentation.

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Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis.

Abha Maheshwari, Shilpi Pandey, Ashalatha Shetty … (2012)

To perform a systematic review and meta-analysis of obstetric and perinatal complications in singleton pregnancies after the transfer of frozen thawed and fresh embryos generated through IVF. Systematic review. Observational studies, comparing obstetric and perinatal outcomes in singleton pregnancies subsequent to frozen thawed ET versus fresh embryo transfer, were included from Medline, EMBASE, Cochrane Central Register of Clinical Trials, DARE, and CINAHL (1984-2012). Women undergoing IVF/intracytoplasmic sperm injection (ICSI). Two independent reviewers extracted data and assessed the methodological quality of the relevant studies using critical appraisal skills program scoring. Risk ratios and risk differences were calculated in Rev Man 5.1. Subgroup analysis was performed on matched cohort studies. Antepartum hemorrhage, very preterm birth, preterm birth, small for gestational age, low birth weight, very low birth weight, cesarean section, congenital anomalies, perinatal mortality, and admission to neonatal intensive care unit. Eleven studies met the inclusion criteria. Singleton pregnancies after the transfer of frozen thawed embryos were associated with better perinatal outcomes compared with those after fresh IVF embryos. The relative risks (RR) and 95% confidence intervals (CI) of antepartum hemorrhage (RR = 0.67, 95% CI 0.55-0.81), preterm birth (RR = 0.84, 95% CI 0.78-0.90), small for gestational age (RR = 0.45, 95% CI 0.30-0.66), low birth weight (RR = 0.69, 95% CI 0.62-0.76), and perinatal mortality (RR = 0.68, 95% CI 0.48-0.96) were lower in women who received frozen embryos. Although fresh ET is the norm in IVF, results of this systematic review of observational studies suggest that pregnancies arising from the transfer of frozen thawed IVF embryos seem to have better obstetric and perinatal outcomes. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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Birth Weight Reference Percentiles for Chinese

Li-Chun Dai, Changfei Deng, Yanhua Li … (2014)

Objective To develop a reference of population-based gestational age-specific birth weight percentiles for contemporary Chinese. Methods Birth weight data was collected by the China National Population-based Birth Defects Surveillance System. A total of 1,105,214 live singleton births aged ≥28 weeks of gestation without birth defects during 2006–2010 were included. The lambda-mu-sigma method was utilized to generate percentiles and curves. Results Gestational age-specific birth weight percentiles for male and female infants were constructed separately. Significant differences were observed between the current reference and other references developed for Chinese or non-Chinese infants. Conclusion There have been moderate increases in birth weight percentiles for Chinese infants of both sexes and most gestational ages since 1980s, suggesting the importance of utilizing an updated national reference for both clinical and research purposes.

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Author and article information

Contributors

Yingying Qin:

ORCID: http://orcid.org/0000-0002-0319-7799

qinyingying1006@163.com

Journal

Journal ID (nlm-ta): Reprod Biol Endocrinol

Journal ID (iso-abbrev): Reprod. Biol. Endocrinol

Title: Reproductive Biology and Endocrinology : RB&E

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-7827

Publication date (Electronic): 4 May 2020

Publication date PMC-release: 4 May 2020

Publication date Collection: 2020

Volume: 18

Electronic Location Identifier: 36

Affiliations

[1 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, Center for Reproductive Medicine, , Shandong University, ; No.157 Jingliu Road, Jinan, China

[2 ]National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China

[3 ]GRID grid.27255.37, ISNI 0000 0004 1761 1174, The Key Laboratory of Reproductive Endocrinology (Shandong University) Ministry of Education, ; Jinan, China

[4 ]GRID grid.460018.b, ISNI 0000 0004 1769 9639, Shandong Provincial Hospital Affiliated to Shandong University, ; Jinan, China

Author information

Yingying Qin http://orcid.org/0000-0002-0319-7799

Article

Publisher ID: 601

DOI: 10.1186/s12958-020-00601-3

PMC ID: 7199365

PubMed ID: 32366332

SO-VID: eefad4b8-7321-4243-a8da-88a68c1c62d9

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 22 January 2020

Date accepted : 24 April 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100012166, National Basic Research Program of China (973 Program);

Award ID: 2017YFC1001100

Award Recipient : Yingying Qin

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81771541

Award ID: 81701404

Award Recipient : Yingying Qin

Funded by: Science Foundation for Distinguished Young Scholars of Shandong

Award ID: JQ201720

Award Recipient : Yingying Qin

Custom metadata

ScienceOpen disciplines: Human biology

Keywords: frozen embryo transfer,endometrial preparation,maternal and neonatal complications,natural cycle,hormone replacement therapy,ovulation induction cycle

Data availability:

ScienceOpen disciplines: Human biology

Keywords: frozen embryo transfer, endometrial preparation, maternal and neonatal complications, natural cycle, hormone replacement therapy, ovulation induction cycle

Increased risk of maternal and neonatal complications in hormone replacement therapy cycles in frozen embryo transfer

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Most cited references 33

The uterine spiral arteries in human pregnancy: facts and controversies.

Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis.

Birth Weight Reference Percentiles for Chinese

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