P-388 The science of frozen embryo transfer, is modified natural cycle better?
Authors: HamZe H , Alameh W , Hemmings R , Jamal W , Banan A , Sylvestre C 
Published: July 2024

Study question

Do live birth rate, obstetric outcomes and number of clinic visits differ between frozen embryo transfer in modified natural and artificial cycle?

Summary answer

Modified natural cycle yielded a higher live birth rate for the similar number of visits, less hypertension, but higher rate of gestational diabetes.

What is known already

A frozen embryo transfer in a modified natural cycle entails procedure timing such that it coincides with the woman’s ovulatory cycle. Conversely, a frozen embryo transfer in an artificial cycle involves controlled hormonal stimulation, with the subsequent scheduling of embryo transfer. Based on the current evidence, there is no difference in pregnancy rates between modified natural cycle and artificial cycle. Frozen embryo transfer during an artificial cycle allows for greater flexibility for the patient and physicians. However, it seems to be associated with higher risk of adverse obstetric and neonatal outcomes.

Study design, size, duration

1206 frozen embryo transfer cycles between January 1st, 2022, and December 31st, 2022 were retrospectively studied. Patients older than 40, with recurrent implantation failure, and recurrent pregnancy loss were excluded. Patients were divided according to their age, BMI, AMH, and the type of embryo transfer protocol. Compared outcomes were endometrial thickness, biochemical pregnancy rate, clinical pregnancy rate, miscarriage rate, number of clinic visits prior to transfer, obstetric complications, livebirth rate, and livebirth weight.

Participants/materials, setting, methods

Patients in the modified natural cycle group were followed by ultrasound and when the endometrium reached a thickness ≥ 7mm, and a dominant follicle ≥ 15 mm, HCG trigger was given, and the embryo (blastocyst) transferred 7 days later. In the artificial cycle group, patients received estrogen supplementation either orally or by patches and when the endometrium reached a thickness ≥ 7 mm, embryo transfer was scheduled following intramuscular progesterone administration for 6 days.

Main results and the role of chance

Patients with modified natural cycle (n = 250) embryo transfers have better clinical pregnancy rate compared to the embryo transfers (n = 250) in artificial cycles (63,6% vs 55,2% p = 0,05), and significantly better live birth rate (57,2% vs 43,9% p = 0,003) despite similar biochemical pregnancy rate (64% vs 61% p = 0,48). The miscarriage rate was significantly lower in modified natural compared to artificial cycles (10,2 % vs 20,99%, p = 0,008). Similar results were found with the transfer of PGTA tested embryos. There was no difference in the endometrial thickness between the 2 groups. The number of visits was higher in the modified natural cycle group, but the difference was not clinically significant (1,57 days vs 1,2 days). When comparing the obstetric outcomes, patients with a modified natural cycle transfer had a lower risk of hypertension (6,6% vs 13,5 % p = 0,10), but a significantly higher risk of gestational diabetes (19% vs 8,3% p = 0,02). No difference was observed regarding the birth weight, percentage of preterm birth or mode of delivery. Regression analysis was performed to identify any cofounder that might have affected the clinical pregnancy rate, and the results showed that the type of transfer was the only factor affecting the outcomes (OR: 1,23 CI: 1,03- 1,46)

Limitations, reasons for caution

The main limitation of this study is its retrospective nature. A randomized controlled study should be performed to confirm these findings.

Wider implications of the findings

Modified natural embryo transfer could be used to improve pregnancy outcomes. With proper scheduling, embryo transfer could be done with a similar number of visits for modified natural cycles and artificial cycles. More studies are needed to assess the increased risk of gestational diabetes with natural cycle embryo transfer.

Trial registration number

NCT06053827