Abstract
Background
In frozen embryo transfer (FET), there is limited consensus on the best means of endometrial preparation in terms of the reproductive outcomes in women with polycystic ovary syndrome (PCOS). The present study aimed to compare the pregnancy and neonatal outcomes following artificial cycle FET (AC-FET) with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment among women with PCOS.
Methods
A total of 4503 FET cycles that satisfied the inclusion criteria were enrolled in this retrospective cohort study between 2015 and 2020. The GnRH-a group received GnRH-a pretreatment while the AC-FET group did not. Propensity score matching (PSM) method and multivariate logistic regression analysis were performed to adjust for potential confounding factors.
Results
After PSM, women in the GnRH-a group suffered a significantly lower miscarriage rate (11.2% vs. 17.1%, P = 0.033) and a higher live birth rate (LBR) compared with those in the AC-FET group (63.1% vs. 56.8%, P = 0.043). No differences were observed in the rates of biochemical pregnancy, clinical pregnancy and ectopic pregnancy between the two groups. A higher mean gestational age at birth was observed in the GnRH-a group than in the AC-FET group (39.80 ± 2.01 vs. 38.17 ± 2.13, P = 0.009). The incidence of neonatal preterm birth (PTB) in the GnRH-a group was lower than that in the AC-FET group (7.4% vs. 14.9%, P = 0.009). Singleton newborns conceived after GnRH-a group were more likely to be small for gestational age (SGA) than those born after AC-FET group (16.4% vs. 6.8%, P = 0.009). However, no significant differences were found between the two groups in terms of mean birthweight, apgar score, the rates of macrosomia, large for gestational age and low birth weight.
Conclusion(s)
In women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with a higher live birth rate and a reduced risk of neonatal PTB. However, there was a concomitant increase in the risk of develo** SGA babies.
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Background
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, accounting for about 70% of anovulatory infertility [1]. Among the strategies for the treatment of infertile PCOS women, frozen embryo transfer (FET) may achieve a higher live birth rate and reduce the risk of ovarian hyperstimulation syndrome (OHSS) compared with fresh embryo transfer [2]. Hence, the application of FET has been recommended as a relatively effective and safer treatment method for this group of infertility patients [3].
Multiple endometrial preparation (EP) cycle protocols have been designed to provide an optimal endometrial environment for embryo implantation in a FET program [4]. However, there is limited consensus on the best means of EP in terms of the reproductive outcomes in women with PCOS [5]. Since PCOS is associated with ovulation dysfunction and irregular menstrual cycles, the most appropriate and frequently used cycle protocol is the artificial cycle FET (AC-FET) [6]. In AC-FET, the endometrium is artificially prepared through consecutive administration of exogenous estrogen and progesterone with or without gonadotropin-releasing hormone agonist (GnRH-a) pretreatment to simulate the natural endocrine environment of the endometrium [7].
GnRH-a is a gonadotropin-releasing hormone (GnRH) analogue with high affinity for pituitary GnRH receptors. After administration, GnRH-a binds to pituitary GnRH receptors and transiently inhibits the hypothalamic–pituitary–gonadal axis, inducing a hypo-estrogenic state [8]. Lower estrogen levels after down-regulation could prevent spontaneous ovulation and prolong the opening period of the “implantation window” to a certain extent [9, 10]. This might be beneficial to the pregnancy outcomes for women undergoing FET.
In assisted reproductive technology (ART), GnRH-a pretreatment combined with AC-FET was found to improve the live birth rate in patients with endometriosis and adenomyosis [11, 30]. However, further studies are needed to validate these findings and clarify the underlying mechanisms.
Strengths and limitations
To the best of our knowledge, this is the largest population study in this field to assess pregnancy-related outcomes following AC-FET with or without GnRH-a pretreatment in women with PCOS. Unlike previous studies that mainly focused on live birth, our study also provided more complete information on the effectiveness and safety of GnRH-a pretreatment by analyzing the neonatal outcomes in PCOS women. Additionally, our study included extensive control for potential confounding differences between GnRH-a and the routine AC-FET groups via PSM and multivariate logistic regression models, thus creating two similar cohorts.
We acknowledge that in this study, we did not obtain information about pregnancy complications, such as gestational hypertension, preeclampsia, and gestational diabetes, which are potential risk factors for adverse neonatal outcomes [39, 40]. This may have a confounding effect on the results. Another limitation is that the neonatal data were obtained through telephone follow-up,which might have led to some information bias.
Conclusions
Our study demonstrated that in women with PCOS who underwent AC-FET, GnRH-a pretreatment was significantly associated with an increase in LBR and a reduced risk of neonatal PTB. However, the incidence of newborns being SGA was also significantly increased at the same time. Therefore, before applying the GnRH-a pretreatment regimen in PCOS women, it seems necessary to take some measures to reduce the risk of neonatal SGA events. Further studies are needed to verify our findings and clarify the underlying mechanisms.
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- FET:
-
Frozen embryo transfer
- GnRH-a:
-
Gonadotropin-releasing hormone agonist
- PCOS:
-
Polycystic ovary syndrome
- AC-FET:
-
Artificial cycle FET
- PSM:
-
Propensity score matching
- LBR:
-
Live birth rate
- GA:
-
Gestational age
- LBW:
-
Low birthweight
- PTB:
-
Preterm birth
- SGA:
-
Small for gestational age
- LGA:
-
Large for gestational age
- OHSS:
-
Ovarian hyperstimulation syndrome
- EP:
-
Endometrial preparation
- ART:
-
Assisted reproductive technology
- PGT:
-
Preimplantation genetic testing
- PGS:
-
Preimplantation genetic screening
- E2:
-
Estradiol
- FSH:
-
Follicle-stimulating hormone
- LH:
-
Luteinizing hormone
- hCG:
-
Human chorionic gonadotropin
- OR:
-
Odds ratio
- CI:
-
Confidence interval
- BMI:
-
Body mass index
- HPO:
-
Hypothalamus-pituitary-ovary
- P:
-
Progesterone
- AFC:
-
Antral follicle count
- AMH:
-
Anti-Mullerian hormone
- SD:
-
Standard deviation
- IQR:
-
Inter-quartile range
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Acknowledgements
We would like to acknowledge all the participants of this project and the medical staff for their contribution to this work.
Funding
This research was supported by funds from Chongqing medical scientific research project (nos:2022QNXM042), Natural Science Foundation of Chongqing (nos:cstc2021jcyj-msxmX0900) and National Natural Science Foundation of China (NO. 82104923).
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YW and WH performed the data collection, statistical analyses and drafted the manuscript. YQ and MC contributed to data collection. QW, XM, XT, QF and YD were responsible for data acquisition and collection. TL and EA participated in the interpretation of the data and critical revision. ZZ, LG and XL designed the study and directed implementation. All authors were involved in revising the article and have approved this final version.
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This study was approved by the Institutional Ethics Committee of Chongqing Medical University. Since this is a retrospective investigation, patients were not asked to participate in this study.
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Wang, Y., Hu, WH., Wan, Q. et al. Effect of artificial cycle with or without GnRH-a pretreatment on pregnancy and neonatal outcomes in women with PCOS after frozen embryo transfer: a propensity score matching study. Reprod Biol Endocrinol 20, 56 (2022). https://doi.org/10.1186/s12958-022-00929-y
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DOI: https://doi.org/10.1186/s12958-022-00929-y