COMMENTARY

Does Use of Frozen Oocytes Affect Obstetric or Perinatal Outcomes?

Peter Kovacs, MD, PhD

Disclosures

November 07, 2014

Obstetric and Perinatal Outcome of Babies Born From Vitrified Oocytes

Cobo A, Serra V, Garrido N, Olmo I, Pellicer A, Remohi J
Fertil Steril. 2014;102:1006-1015

Background

Assisted reproductive technology (ART) has undergone tremendous improvements since the announcement of the first birth following the use of in vitro fertilization (IVF) in 1978.[1] Embryo cryopreservation, donor gamete use, surrogacy, embryo screening for genetic problems, and, more recently, oocyte and ovarian tissue cryopreservation are procedures available through ART.

The first successful pregnancy following oocyte cryopreservation was reported in 1986.[2] The wider availability of oocyte freezing, however, was not a reality until much later, due to technical problems related to the procedure. Mature oocytes are sensitive to cryoinjury, and survival rates and subsequent fertilization and embryo development rates were not acceptable. Technological improvements and the introduction of vitrification, however, have been associated with significant improvements in oocyte cryopreservation. With the current technology, around 90% of the oocytes survive the freezing-thawing process.[3] On the basis of the latest results, in 2013, fertility societies reclassified oocyte cryopreservation as no longer experimental.[4]

Who are the patients who could benefit from this technology? Oocyte cryopreservation is primarily recommended for patients who are diagnosed with cancer and wish to preserve their fertility prior to starting gonadotoxic therapy. Patients with medical conditions (chronic autoimmune diseases, severe endometriosis) who can expect to undergo surgical or medical interventions that may compromise ovarian function are also candidates. Eggs can be cryopreserved during standard IVF treatments as well when the partner is unable to provide sperm on the day of egg retrieval or when, for ethical reasons, the couple wants to limit the number of eggs fertilized.

Egg freezing makes it possible to set up egg banks of donor oocytes where the regulations require anonymous donation. Finally, egg donation can be considered for later self-use when a patient, for various reasons, decides to delay childbearing.

As with any new technology, its safety has to be established. This paper reports on obstetric and perinatal outcomes with the use of vitrified oocytes.

The Study

The report is a retrospective analysis based on treatments involving fresh and frozen oocytes from a single fertility center. Data were available based on reports from about 80% of the women undergoing treatment. The lack of complete response rate from those treated limited the sample size to 1224 children born following the use of fresh oocytes and 1027 children born following the use of vitrified oocytes. The use of own and donated oocytes was analyzed together and separately as well. Data were collected for patient and treatment characteristics, and confounding variables were controlled for during the analysis. Women using vitrified oocytes were slightly older, were more likely to have previous miscarriages, and had fewer prior term deliveries. They also were more likely to be poor responders; therefore, donor egg use was more frequent among them. The number of mature oocytes was higher in the fresh oocyte group.

Of the pregnancies using fresh oocytes, 77.1% were singletons, while the corresponding figure was 72.6% in the vitrified oocyte group. The rate of vanishing twins was comparable. Data were not provided on first or early second trimester losses. Gestational age at delivery, birth weight, and the risk for low birth weight and small-for-gestational-age were comparable. The incidence of minor and major birth defects did not differ between the groups, and the need for intensive care unit admission was also similar. The risk for medical problems during pregnancy was comparable between the groups.

When the analysis was limited to the use of own oocytes, there was still no difference in the obstetric and perinatal outcomes between the fresh and vitrified oocyte groups. The only difference was a slightly higher rate of minor anomalies, but this observation was based on a total of five cases only. When comparisons were made for multiple pregnancies using own oocytes or singleton or multiple pregnancies using donated oocytes, there were no differences in obstetric and perinatal outcomes with fresh vs vitrified oocytes.

The authors concluded that, on the basis of their experience, the use of oocyte vitrification was not associated with higher obstetric or perinatal risks.

Uses for Cryopreservation

Currently, the most widely accepted indication for oocyte cryopreservation is for fertility preservation prior to oncologic therapy. Oocyte vitrification is associated with over 90% survival rate and continuously improving pregnancy rates. A 2011 meta-analysis compared treatment outcomes with fresh, vitrified, and slow-frozen oocytes based on the results of five studies. Fertilization and cleavage rates, the availability of top-quality embryos, and clinical pregnancy rates were comparable with fresh and vitrified oocytes. Vitrification was superior for all of these parameters over slow-freezing.[5] Goldman and colleagues found no difference in the live birth rate when they analyzed treatment outcomes with fresh or frozen oocytes.[6]

In addition, Di Pietro and colleagues[7] found no adverse effect on the biomolecular quality of vitrified oocytes. Noyes and colleagues[8] reported a congenital anomaly rate of 1.3% with the use of frozen-thawed oocytes, which was not different from the rate observed in natural conceptions. Levi Setti and colleagues[9] reported a similar rate of fetal anomalies with frozen vs fresh oocytes but a higher rate of miscarriages with frozen oocytes (26.9% vs 17.6%). They observed no difference in the mean gestational age at delivery, but the mean birth weight was lower in both singleton and twin pregnancies in the group where fresh eggs were used.

Egg vitrification is often used by large donor egg programs. The availability of frozen-thawed donor oocytes makes it possible to guarantee anonymous donation and continuous care without the need to synchronize the donor and the recipient.

Another increasingly used indication for oocyte cryopreservation is social oocyte freezing. Women who wish to delay childbearing for work or educational reasons or until they find the right partner may elect to cryopreserve oocytes for later use. This way they can use younger, healthier eggs even when they are in their 40s. It should be emphasized, however, that pregnancy outcome may not be the same due to uterine or medical problems that are more likely to occur at an older age. The results of this study regarding obstetric and perinatal complications cannot be applied to them because they would need to be compared with women conceiving spontaneously in their 20s or early 30s.

Viewpoint

The findings of this study are reassuring. The authors used a large sample size from a single institution, and this is certainly a strength of the study. One weakness, however, is that they did not have information on all of the patients, and this could have biased their results, especially regarding those parameters where small numbers were reported, such as for congenital anomalies. Furthermore, they did not collect data on pregnancy outcome before the 24th week. A higher miscarriage rate and pregnancy termination due to abnormal screening results may also affect some of the parameters reported. It also needs to be emphasized that in close to three fourths of the cycles, donated eggs were used. Because an egg donor has to be a healthy, young, fertile woman, her eggs are expected to be of higher quality. Results obtained with such eggs cannot necessarily be applied to the infertile population or to cancer patients. A subanalysis of data regarding own eggs was performed, but in that case the number of cases and controls was obviously much lower.

Further data will need to be collected on obstetric and perinatal outcomes as well as early and later childhood development following the use of vitrified oocytes. It is, however, reassuring at this stage that, based on the available information, no harmful effects have been observed with this technology.

Abstract

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