Article
Spontaneous ovulation versus HCG triggering for timing natural-cycle frozen–thawed embryo transfer: a randomized study

https://doi.org/10.1016/j.rbmo.2011.06.004Get rights and content

Abstract

In ovulatory patients, frozen–thawed embryo transfer (FET) is commonly performed during a natural cycle (NC). The objective was to compare serial monitoring until documentation of ovulation with human chorionic gonadotrophin (HCG) triggering, for timing NC-FET. Sixty women with regular menstrual cycles undergoing NC-FET were randomized into two groups: group A (n = 30) had FET in a natural cycle after ovulation triggering with HCG; group B (n = 30) had FET in a natural cycle after detection of spontaneous ovulation. The main outcome measure was the number of monitoring visits at the clinic per cycle. Secondary outcome measures included implantation rate, clinical pregnancy and live-birth rates. Both groups were similar in terms of demographic characteristics and reproductive history. Clinical and laboratory characteristics of fresh and frozen cycles and pregnancy and delivery rates were comparable for both groups. The number of monitoring visits in group A (3.2 ± 1.4) was significantly lower than in group B (4.7 ± 1.6) (P = 0.002). In patients undergoing NC-FET, triggering ovulation by HCG can significantly reduce the number of visits necessary for cycle monitoring without an adverse effect on cycle outcome. Ovulation triggering can increase both patient convenience and cycle cost effectiveness.

In patients with regular cycles, frozen–thawed embryo transfer (FET) is commonly performed during a natural cycle (NC). The objective was to compare serial monitoring until documentation of ovulation with human chorionic gonadotrophin (HCG) triggering, for timing NC-FET. Sixty women with regular menstrual cycles undergoing NC-FET were randomized into two groups: group A (n = 30) had FET in a natural cycle after ovulation triggering with HCG; group B (n = 30) had FET in a natural cycle after detection of spontaneous ovulation. The main outcome measure was the number of monitoring visits at the clinic per cycle. Secondary outcome measures included pregnancy and live birth rates. Patients in both groups were similar in terms of demographic characteristics and reproductive history. Clinical and laboratory characteristics of fresh and frozen cycles were also found comparable for both groups, as were pregnancy and delivery rates. The number of monitoring visits in group A (3.2 ± 1.4) was significantly lower than in group B (4.7 ± 1.6) (P = 0.002). Thus, each patient that received HCG had saved approximately 1.5 visits at the clinic in preparation for FET. In patients undergoing NC-FET, triggering ovulation by HCG can significantly reduce the number of visits necessary for cycle monitoring without an adverse effect on cycle outcome. Ovulation triggering can increase both patient convenience and cycle cost effectiveness.

Introduction

Cryopreservation of supernumerary embryos following IVF has become an important feature in assisted reproduction technology and is widely practiced as a safe and cost-effective method to increase cumulative pregnancy rates per oocyte retrieval. The current trend towards decreasing the number of embryos being transferred and the increased implementation of single-embryo transfer (SET) policy in many IVF programmes emphasize the relevance and importance of frozen–thawed embryo transfer (FET).

Synchronization between embryonic and endometrial development is a major consideration in preparation for FET. Care needs to be taken so that the age of the embryos after thawing corresponds to the age of the endometrium on the day of embryo transfer. FET has been carried out through different cycle regimens including: spontaneous ovulatory cycles (natural cycle); cycles in which ovulation is induced by drugs (ovulation induction cycle); and cycles in which the endometrium is artificially prepared by exogenous oestrogen and progesterone (artificial cycle). All regimens seem to be similar in their efficacy. A recent Cochrane review comparing cycle regimens for FET has concluded that at the present time there is insufficient evidence to support the use of one intervention in preference to another (Ghobara and Vandekerckhove, 2008).

In ovulatory patients, FET is commonly performed during a natural cycle (NC) (Byrd, 2002). The NC offers the advantages of utilizing the natural physiological process of endometrial preparation for implantation and decreases medical intervention as compared with hormone replacement or stimulated cycles. These advantages make NC-FET preferable to many women. For the purpose of synchronization between the endometrium and the frozen embryos, the day of spontaneous ovulation in the NC corresponds to the day of egg retrieval in the ‘fresh’ IVF cycle. Thawing and transferring of embryos is scheduled according to the stage at which embryos were frozen. Patient monitoring prior to FET in a NC consists of serial blood and ultrasound testing until the detection of ovulation (al-Shawaf et al., 1993). Alternatively, human chorionic gonadotrophin (HCG) may be utilized to trigger ovulation in the presence of a mature follicle and satisfactory endometrial development. This latter approach may simplify the monitoring process by saving the patients and the clinic the time and expense involved in extra visits necessary for documentation of ovulation.

A recent retrospective study compared serial monitoring until documentation of ovulation, with HCG triggering, for timing FET in natural cycles (Weissman et al., 2009). It was demonstrated that triggering ovulation by HCG can significantly reduce the number of visits necessary for cycle monitoring without an adverse effect on cycle outcome.

In order to validate these findings, this study conducted a randomized trial focusing on the same outcome measures. The aim was to compare the number of clinic visits and cycle outcome between ovulation triggering by HCG and serial monitoring until documentation of ovulation in patient preparation for NC-FET.

Section snippets

Materials and methods

The study design was a prospective, randomized trial conducted at a tertiary referral university hospital.

Results

In group A, five patients did not meet the criteria for HCG administration and were withdrawn from the study. Of the 25 left, only one had no embryos available for transfer after thawing. In group B, all patients completed the study and 27 had FET. In three patients there were no embryos available for transfer after thawing.

Demographic characteristics and reproductive history of patients in groups A and B were similar (Table 1). The fresh cycles leading to embryo freezing were found comparable

Discussion

This study suggests that triggering of ovulation with HCG is as efficient as serial monitoring until ovulation detection in patient preparation for NC-FET in terms of implantation, pregnancy and live-birth rates. Since ovulation triggering by HCG significantly reduces the number of monitoring visits that are necessary to schedule the day of FET, this approach may be superior in terms of patient convenience and cost-effectiveness of the cycle.

For many years, FET has been successfully performed

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Dr Ariel Weissman graduated from the Hadassah-Hebrew University Medical School in Jerusalem in 1988. In 1994 he completed his residency in obstetrics and gynaecology at the Kaplan Medical Centre, Rehovot, where he spent another 2 years working as a senior physician in the IVF unit. He then pursued a 2-year research and clinical fellowship with Bob Casper at the Division of Reproductive Sciences, University of Toronto, Canada. His main focus of research was transplantation of human ovarian tissue in immunodeficient mice. In 1998, he joined the IVF unit at the Wolfson Medical Centre, where he currently holds a position of senior lecturer.

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