The effects of age, mature oocyte number, and cycle number on cumulative live birth rates after planned oocyte cryopreservation

As use of OC increases, outcome data must be published so patients can make educated decisions about how to best employ this technology to preserve their fertility. Patients must be counselled that younger age at OC and more mature oocytes improve cumulative live birth rates. However, additional OC cycles from different months do not independently improve cumulative live birth rates. The benefit of additional OC cycles can be explained by the increased number of oocytes. Our results provide more information about the CLBR from OC based on age at OC and number of cryopreserved oocytes. This data can help patients decide how many oocytes to cryopreserve.

We provide a CLBR per patient, which is the most useful parameter when counselling OC patients. Our model, which predicts CLBR based on age at OC and total number of M2s thawed can help physicians provide personalized patient counselling. This information not only arms patients with realistic expectations, but can also help them decide whether to pursue additional OC cycles to obtain more oocytes. For example, a 34 year-old patient with 10 M2s from her first OC cycle can be counseled that cryopreserving 10 additional M2s will improve CLBR from approximately 49% to approximately 66%.

The optimal number of oocytes to cryopreserve varies for each patient. This number is not only influenced by the age at OC, but also by the patient’s ovarian reserve, desired likelihood of success, family building goals, and financial situation. Counseling must be individualized, but the predicted CLBRs from our models can help patients decide whether they would benefit from additional oocytes from additional OC cycles. Younger patients with a high number of oocytes from their first OC cycle may decide that the risks and cost of additional OC cycles outweigh the benefits.

Due to the time delay between OC and oocyte thaw, 38% of patients in this cohort underwent their first OC cycle between 2004 and 2012. OC was experimental during this time, and was not covered by employers or insurance. Due to the experimental nature and high cost of OC, patients who obtained a reasonable number of oocytes during their first OC cycle rarely pursued additional OC cycles. By contrast, patients who obtained a small number of oocytes during their first OC cycle often chose to pursue additional OC cycles to increase their chance of live birth. Now that OC is no longer considered experimental and is sometimes covered by employers or insurance, more patients with a reasonable number of oocytes from their first OC cycle are electing to pursue additional OC cycles.

This study does not provide information about the chance of achieving a second live birth from OC because most of our patients with one live birth from OC have not yet returned to use their remaining embryos. However, we report 50 patients with ≥ 2 children from OC, and the fact that 57% of patients had remaining cryopreserved oocytes and euploid/untested embryos from OC after one live birth suggests that many patients can build larger families from OC.

It is also important to note that our study includes oocytes that were slow-frozen in addition to those that were vitrified. Although our center now exclusively uses vitrification to cryopreserve oocytes, previous data from our center demonstrates that our slow-frozen oocytes performed very well [1, 11]. At our center, the decision to use vitrification alone was primarily due to laboratory efficiency, rather than improved outcomes with this cryopreservation method.

One major strength of this study is that it uses real OC data, rather than data based on IVF patients and oocyte donors. Our CLBRs for younger patients are lower than the CLBRs predicted by both Fox and Goldman.’s [12] and Maslow et al.’s [10] models. For example, Fox and Goldman’s model predicts that patients who undergo OC at age 34 and cryopreserve 6, 12, 18, and 24 M2s have CLBRs of 50%, 75%, 88%, and 94% respectively, while our model predicts respective CLBRs of 42%, 52%, 62%, and 71% for these patients. Similarly, Maslow et. al’s model predicts that women aged < 35 years have a 70% estimated live birth rate when 10 M2s are obtained from their first retrieval and a 80% predicted live birth rate when 17 M2s are obtained from their first retrieval, while our model predicts lower live birth rates for women, especially as they approach 35 years. Therefore, we suggest that OC models that rely on extrapolated data from IVF patients with normal ovarian reserve and oocyte donors be used with caution because they likely overestimate CLBRs for younger patients. We recommend using data from real OC patients for patient counseling.

This study is limited because Anti-Müllerian Hormone (AMH), Body Mass Index (BMI), and race/ethnicity were not included in our analysis and may impact the number of oocytes retrieved and live birth rates. This study is also limited by the relatively small number of OC patients who have returned for thaw. Many OC patients do not return to use their cryopreserved oocytes, and those who do return to use their cryopreserved oocytes tend to return several years later [13, 14]. Moreover, the majority of patients (72%) in this study only underwent 1 OC cycle. Larger studies are required to corroborate our findings about the effect of cycle number and to more precisely detect differences in CLBR based on age at OC and number of M2s. Moreover, this study includes patients who underwent oocyte thaw at a single high-volume urban university-affiliated institution and may not be generalizable to other OC patients. Further studies are needed from a variety center types and locations.

In conclusion, the number of cryopreserved M2s predicts CLBR, even at young ages. However, additional OC cycles do not independently improve cumulative live birth rates. This study is the first report of oocyte thaw outcomes to examine the influence of OC cycle number on CLBR, and suggests that additional OC cycles do not increase CLBR beyond increasing oocyte quantity. Our results can help OC patients estimate their CLBR and decide whether to pursue additional OC cycles to obtain more oocytes.

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