O-025 Livebirth delivery rates after natural versus artificial cycle in women receiving donated oocytes and the impact of female age.
Authors: Rafael F , David B , Mascarós Martínez J , Neves A , Labarta E , Garrido N , Nunes S , Garcia-Velasco J A , Reis Soares S , Santos-Ribeiro S 
Published: June 2023

Study question

Is female age associated with worse outcomes following embryo transfer in either a natural cycle (NC) or artificial cycle (AC) in women receiving donated oocytes?

Summary answer

NC embryo transfers resulted in both lower miscarriage and higher livebirth rates, and the age of the female recipient did not modify this effect.

What is known already

Previous studies have demonstrated that NC may result in better outcomes than AC embryo transfer. When feasible, avoiding AC in advanced maternal age and/or couples using donated oocytes could be considered, given the potential compounding effect for certain negative maternal and perinatal outcomes such as gestational hypertension. However, there is limited research on the use of NCs in women of advanced maternal age and research thus far has shown that the luteal phase of the menstrual cycle in older women may be altered, thus potentially limiting the effectiveness of NC.

Study design, size, duration

This retrospective, multicentre, cohort study included all single blastocyst embryo transfers following oocyte donation performed between January 2010 and December 2019, subdivided according to the type of endometrial preparation performed (NC or AC). The oocyte donation model was preferred to minimize the potential confounding effect related to both poor embryo quality in older women and the influence that ovarian stimulation performed during autologous IVF may have on endometrial receptivity prior to a fresh embryo transfer.

Participants/materials, setting, methods

The main objective of the study was to compare livebirth delivery rates (LBR). The secondary outcomes included hCG positive pregnancy rate, clinical pregnancy rate (CPR) and miscarriage rate. Confounder-adjustment was performed using multivariable generalized estimating equations model regression analysis, adjusting for multiple confounders. Additionally, an interaction variable was added to the final multivariable model to assess whether female recipient age may modify the effect of each type of endometrial preparation on LBRs.

Main results and the role of chance

In total, 38259 embryo transfers were analysed, including AC (n = 34850) and NC (n = 3409). Mean recipient age was 42 years, with a range of 20-50 years. The results showed that despite being associated with a higher hCG positive pregnancy (57.1% vs 53.5%; OR 0.91 CI 0.84-0.98), AC were also associated with a higher miscarriage rate per hCG positive pregnancy (33.5% vs 27.9%; OR 0.70 CI 0.62-0.78) when compared to NC, resulting in slightly lower LBRs per transfer with AC (38.0% vs 38.6%; OR 1.13 CI 1.05-1.21). All primary and secondary outcomes were still significant following confounder adjustment. Confounder variables included were female donor and recipient age, recipient BMI, female factor infertility, male factor infertility, number of mature oocytes donated, oocyte status (fresh versus vitrified), sperm source (partner or donor), embryo status (fresh versus vitrified), embryo quality, endometrial thickness, and year of transfer. The interaction of endometrial preparation method with female recipient age was not statistically significant (aOR 1.02, 95% CI 0.99-1.05).

Limitations, reasons for caution

The retrospective nature of the study and the inherent risk of bias related to confounding may have impacted the results. Another limitation is the low numbers of natural cycles (9% of all cycles), which could be related to the low uptake to the treatment and/or to selection bias.

Wider implications of the findings

NC seems slightly better than AC and the differences between the two are unlikely to be modified by female age. Therefore, it seems reasonable to suggest NC for older women, as they would benefit from the decreased risk of miscarriage and hypertension during pregnancy.

Trial registration number

not applicable