COMMENTARY

The Ideal Number of Oocytes for IVF

Peter Kovacs, MD, PhD

Disclosures

February 23, 2015

Can You Ever Collect Too Many Oocytes?

Briggs R, Kovacs G, MacLachlan V, Motteram C, Baker HW
Hum Reprod. 2015;30:81-87

Background

During in vitro fertilization (IVF), the ovaries are stimulated to induce multifollicular development. At the end of this phase, the oocytes are retrieved and are fertilized. As a last step, the embryos are cultured for a few days before they are transferred or cryopreserved.

Another way to perform IVF is via a natural, unstimulated cycle, when the single dominant follicle is monitored, a single egg is collected, and a single embryo is transferred. The benefit of this approach is that the patient is not exposed to daily hormonal injections, one does not have to worry about hyperstimulation, and the costs associated with the treatment are low. The disadvantage of this approach is that eggs cannot be collected from every follicle. On average, only 60%-70% of retrieved oocytes fertilize successfully.[1]

Therefore, if we want to increase the efficacy of the treatment, stimulation is used first. There are multiple stimulation protocols and gonadotropin preparations to choose from. Stimulation is typically tailored to the patient's needs and individualized based on age, ovarian reserve markers, ultrasound findings, body mass index, and response to previous stimulation.[2] In addition, a desired egg yield has to be determined that will lead to good clinical outcome with minimum risk and reduced costs.

The authors of this paper tried to determine what the optimal oocyte yield would be.

The Study

The conclusions were drawn following a retrospective analysis based on IVF treatment data from a 2-year period. The study included 7697 cycles; those in which embryo transfer did not take place were excluded. The analysis was performed on the full dataset and separately involving the first cycles only.

The number of oocytes collected was in the range of 1-48. The live birth rate was 9.2% when a single oocyte was collected and was 31.3% when more than 16 oocytes were available for fertilization.

Logistic regression analysis of the first cycles only (N = 3600) showed that age had a negative impact on live birth rates, while the transfer of blastocyst(s) (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.25-1.95) and an increase in oocyte number (log oocyte number OR, 1.46; 95% CI, 1.03-2.06) were associated with higher chance to achieve live birth.

A second logistic regression analysis was performed on all cycles from the study period (N = 7697). This analysis has also shown that increasing age and the number of previous assisted reproductive technology attempts had a negative impact on IVF outcome. In contrast, previous successful treatment resulting in live birth was associated with a better prognosis (OR, 1.65, 95% CI, 1.40-1.95). The transfer of blastocysts and the transfer of two embryos instead of one were also associated with improved outcome. The number of retrieved oocytes was associated with a significant increase in the live birth rate (log oocyte number OR, 1.48, 95% CI, 1.17-1.86).

Higher oocyte yield was linked to an increase in the proportion of immature oocytes as well as an increase in the availability of surplus embryos for cryopreservation. In the same study period, a 24% live birth rate was achieved through frozen embryo transfer.

The authors concluded that one cannot collect too many oocytes because pregnancy and live birth rates increase with the number of available oocytes.

Viewpoint

With IVF, a goal has to be set that provides the lab with a sufficient number of good-quality eggs but doesn't put the patient at risk for hyperstimulation. Several studies have evaluated the "optimal" egg number. Sunkara and colleagues,[3] for example, have analyzed the outcome of over 400,000 cycles and have found a continuous increase in pregnancy rates up until 15 eggs and a plateau in pregnancy rates beyond that. Van der Gaast and colleagues[4] concluded that 13.1 eggs resulted in optimal outcome based on a smaller database. Steward and colleagues[5] used the Society for Assisted Reproductive Technology registry from 2008 to 2010 to study live birth rates and ovarian hyperstimulation syndrome (OHSS) rates based on 256,381 cycles. There was a continuous increase in live birth rates across the egg categories up until 11-15 oocytes (0-5 oocytes: 17%; 11-15 oocytes: 39.3%). There was, however, no further significant increase in the live birth rates in the higher oocyte yield groups. Receiver operating characteristic analysis determined 15 oocytes as a cut-off above which OHSS risk significantly increased.

Higher egg yield is associated with benefits. Even if we account for an increased proportion of immature oocytes, we still end up with more embryos. This should result in an increase in the number of cycles with cryopreservation and should result in higher cumulative pregnancy rates. On the other hand, the simultaneous development of several follicles will result in supraphysiologic steroid hormone levels that could have an adverse effect on implantation, placentation, and even perinatal outcome.[6] The risk for OHSS, which is a potentially life-threatening complication of ovarian stimulation, also increases with the number of oocytes collected.[5]

Most studies put the optimal number of retrieved oocytes between 10 and 15. Even in the currently discussed study, the increase was less pronounced over 15 oocytes. When we take treatment, perinatal outcomes, and overall expense into consideration, a treatment that results in the collection of around 15 oocytes seems to serve the patient's best interest.

Abstract

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