Related Experiment Video
Updated: Aug 14, 2026

Orthotopic Ovarian Transplantation Procedures to Investigate the Life- and Health-span Influence of Ovarian Senescence in Female Mice
Published on: February 12, 2018
Modified natural cycle vs. hormone replacement therapy embryo transfer in women over 40 years old: a retrospective
Pietro Molinaro1, Elisa Napoleoni2, Carlos Alonso3
1IVIRMA Global Research Alliance, IVI Roma, IVIRMA Roma Affiliation, Rome, Italy; Department of Pediatrics, Obstetrics, and Gynecology, University of Valencia (UV), Valencia, Spain.
Objective:
To compare live birth rate (LBR) and other reproductive outcomes between modified natural cycle embryo transfer (mNC-ET) and hormone replacement therapy embryo transfer (HRT-ET) cycles in women aged ≥40 years undergoing single embryo transfer (SET).
Design:
Observational, retrospective, multicentric cohort study.
Subjects:
A total of 26,039 SETs performed in 16,579 women aged 40-49 years between January 2019 and December 2023 across 21 clinics in Spain and Italy. Only euploid frozen ETs were considered for autologous cycles, whereas both fresh and frozen ETs were included for egg donor cycles.
Exposure:
Endometrial preparation with mNC-ET or HRT-ET protocols.
Main Outcomes Measures:
The primary outcome was LBR. Secondary outcomes included biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), and ongoing pregnancy rate (OPR), and biochemical miscarriage rate (BMR) and clinical miscarriage rate (CMR).
Results:
The study analyzed 26,039 SETs (2,694 mNC-ETs vs. 23,345 HRT-ETs) in 16,579 patients (43.1 ± 2.4 years). Multivariate analysis adjusted for confounders demonstrated comparable LBR (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI]: 0.99-1.24) between mNC and HRT-ET, while mNC-ET was associated with lower risk of clinical miscarriage (aOR 0.58, 95% CI: 0.46-0.73) and higher OPR (aOR 1.14, 95% CI: 1.02-1.26). Subgroup analyses indicated that mNC-ET was associated with a lower risk of clinical miscarriage (aOR 0.47, 95% CI: 0.32-0.68) and a higher likelihood of OPR (aOR 1.24, 95% CI: 1.05-1.47) and live birth (aOR 1.21, 95% CI: 1.02-1.44) among autologous cycles. In donor oocyte cycles, it was associated with a reduced risk of clinical miscarriage (aOR 0.66, 95% CI: 0.49-0.88), and comparable live birth (aOR 1.06 , 95% CI: 0.93-1.22).
Conclusion:
Modified natural cycle embryo transfer was associated with a comparable LBR to that of HRT-ET in women over 40 years old, supporting its feasibility as an endometrial preparation method in this population. Further research should confirm the impact on reproductive outcomes and evaluate potential obstetric benefits in this population.
Related Concept Videos
Menopause
Oogenesis
Ovarian Cycle
In Vitro Fertilization
The IVF process begins with ovarian stimulation, during which reproductive endocrinologists prescribe hormonal medications to stimulate the ovaries to produce multiple eggs instead of the single...