Department of Biomedical Sciences, Humanitas University, Pieve...

Is there an association between the different endometrial preparation protocols for frozen embryo transfer FET and obstetric and perinatal outcomes Programmed FET protocols were associated with a significantly higher risk of hypertensive disorders of pregnancy HDP pre-eclampsia PE post-partum hemorrhage PPH and cesarean section CS when compared with natural FET protocols An important and growing source of concern regarding the use of FET on a wide spectrum of women is represented by its association with obstetric and perinatal complications However reasons behind these increased risks are still unknown and understudied Systematic review with meta-analysis We systematically searched PubMed MEDLINE Embase and Scopus from database inception to 1 November 2021 Published randomized controlled trials cohort and case control studies were all eligible for inclusion The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale The quality of evidence was also evaluated using the Grading of Recommendations Assessment Development and Evaluation GRADE approach Studies were included only if investigators reported obstetric and or perinatal outcomes for at least two of the following endometrial preparation protocols programmed FET cycle PC-FET i e treatment with hormone replacement therapy HRT total natural FET cycle tNC-FET modified natural FET cycle mNC-FET stimulated FET cycle SC-FET Pooled results showed a higher risk of HDP 12 studies odds ratio OR 1 90 95 CI 1 64-2 20 P 0 00001 I2 50 very low quality pregnancy-induced hypertension 5 studies OR 1 46 95 CI 1 03-2 07 P 0 03 I2 0 very low quality PE 8 studies OR 2 11 95 CI 1 87-2 39 P 0 00001 I2 29 low quality placenta previa 10 studies OR 1 27 95 CI 1 05-1 54 P 0 01 I2 8 very low quality PPH 6 studies OR 2 53 95 CI 2 19-2 93 P 0 00001 I2 0 low quality CS 12 studies OR 1 62 95 CI 1 53-1 71 P 0 00001 I2 48 very low quality preterm birth 15 studies OR 1 19 95 CI 1 09-1 29 P 0 0001 I2 47 very low quality very preterm birth 7 studies OR 1 63 95 CI 1 23-2 15 P 0 0006 I2 21 very low quality placenta accreta 2 studies OR 6 29 95 CI 2 75-14 40 P 0 0001 I2 0 very low quality preterm premature rupture of membranes 3 studies OR 1 84 95 CI 0 82-4 11 P 0 14 I2 61 very low quality post-term birth OR 1 90 95 CI 1 25-2 90 P 0 003 I2 73 very low quality macrosomia 10 studies OR 1 18 95 CI 1 05-1 32 P 0 007 I2 45 very low quality and large for gestational age LGA 14 studies OR 1 08 95 CI 1 01-1 16 P 0 02 I2 50 very low quality in PC-FET pregnancies when compared with NC tNC mNC -FET pregnancies However after pooling of ORs adjusted for the possible confounding variables the endometrial preparation by HRT maintained a significant association in all sub-analyses exclusively with HDP PE PPH low quality and CS very low quality The principal limitation concerns the heterogeneity across studies in i timing and dosage of HRT ii embryo stage at transfer and iii inclusion of preimplantation genetic testing cycles To address it we undertook subgroup analyses by pooling only ORs adjusted for a specific possible confounding factor Endometrial preparation protocols with HRT were associated with worse obstetric and perinatal outcomes However because of the methodological weaknesses recommendations for clinical practice cannot be made Well conducted prospective studies are thus warranted to establish a safe endometrial preparation strategy for FET cycles aimed at limiting superimposed risks in women with an a priori high-risk profile for obstetric and perinatal complications None CRD42021249927 The Author s 2022 Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology All rights reserved For permissions please email journals permissions oup com

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy.

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Obstetric and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a system...