Beyond embryos: the uncharted territory of aging endometrium and frozen embryo transfer outcomes in women aged 40 and older.

Maghraby*, Hassan; Gaafar, Sherif; Atef, Aya; Hassan, Heba

doi:10.21608/jrme.2025.361594.1028

	Beyond embryos: the uncharted territory of aging endometrium and frozen embryo transfer outcomes in women aged 40 and older.
Journal of Reproductive Medicine and Embryology
Article 6, Volume 1, Issue 4, February 2025, Page 243-248 PDF (215.07 K)
Document Type: Debate
DOI: 10.21608/jrme.2025.361594.1028
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Authors
Hassan Maghraby* ¹^{, 2}; Sherif Gaafar¹^{, 2}^{, 3}; Aya Atef¹^{, 2}; Heba Hassan²^{, 4}
¹Obstetrics and Gynecology Department, Alexandria University, Egypt.
²Egyptian Foundation of Reproductive Medicine and Embryology, Alexandria, Egypt.
³Madina Fertility Center, Madina Women’s Hospital, Alexandria, Egypt.
⁴Adam and Hawa IVF center. Alexandria, Egypt.
Abstract
As the demand for assisted reproductive technologies continues to rise, frozen embryo transfer (FET) has emerged as a viable option for women seeking to conceive, particularly those over 40. However, the focus on embryo quality and selection has led to a critical oversight: the impact of endometrial aging on FET outcomes. The most controllable factor affecting FET outcomes is the patient’s endometrial condition; thus, improving endometrial receptivity is a research hotspot. Currently, various endometrial preparation protocols before FET have been suggested, including natural cycles (NC), hormone replacement therapy (HRT) cycles, with or without gonadotropin-releasing hormone agonist (GnRHa) down- regulation, and ovulation induction (OI) cycles. However, until now, no consensus exists on the ideal endometrial preparation regimen before FET, especially for elderly women. the success of FET in women over 40 cannot be solely attributed to embryo quality. The endometrium, once considered a passive recipient, plays a critical role in implantation and pregnancy outcomes. For patients with advanced maternal age (AMA), we should consider the most suitable, safe, and effective endometrial preparation protocol based on the epigenetic, molecular, vascular and cellular characteristics of these patients. From the above mentioned evidence, we should be very cautious before using NC-FET in AMA, as the natural cycle is “not completely natural” nor physiologic in these subgroup of patients.
Keywords
advanced maternal age; frozen embryo transfer; endometrial preparation


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