Perinatal outcomes of pregnancies following autologous cryopreserved ovarian tissue transplantation: a systematic review with pooled analysis

OBJECTIVE To synthesize the existing evidence on perinatal outcomes following autologous cryopreserved ovarian tissue transplantation (ACOTT), concurrently identifying key factors influencing these outcomes. DATA SOURCES We performed a comprehensive search of MEDLINE, Embase, and Cochrane Library databases to identify relevant studies on the impact of ACOTT on perinatal outcomes from inception until October 22, 2023. Where there is missing information, the authors were contacted for updated data. STUDY ELIGIBILITY CRITERIA Observational studies, such as cohort studies, case series, and case reports that reported a live birth following ACOTT, were considered eligible. Studies lacking data on women's demographic characteristics, ACOTT procedure details, or perinatal outcomes were excluded. Cases involving fresh or non-autologous transplantations and those addressing primary ovarian insufficiency were also excluded. RESULTS We included 58 studies comprising 122 women with 162 deliveries (154 singletons and 8 twins) after ACOTT, resulting in 170 newborns. Among these women, the majority (83.6%) had a malignant disease. Most of these women were exposed to some chemotherapy before ovarian tissue cryopreservation (OTC) (51%). Of 162 childbirths, 66.7% were naturally conceived, with the remaining 33.3% pregnancies being achieved through assisted reproductive techniques (ART). The birth weight of 88.5% of newborns was appropriate for gestational age, while 8.3% and 3.1% were small- and large-for-gestational-age, respectively. The preterm birth rate was 9.4%, with the remaining being term deliveries. Hypertensive disorders of pregnancy were noted in 18.9% of women, including pregnancy-induced hypertension in 7.6%, pre-eclampsia in 9.4%, and HELLP syndrome in 1.9%. Incidences of gestational diabetes and preterm premature rupture of membranes were 3.8% for each condition. Neonatal anomalies were reported in 3 transplant recipients with 4 newborns: arthrogryposis, congenital cataract, and diaphragmatic hernia in a twin. Finally, among the recipients' characteristics, not receiving chemotherapy before OTC (odds ratio:0.23, 95%CI:0.07-0.72, P-value:0.012) and natural conception (odds ratio:0.29, 95%CI:0.09-0.92, P-value:0.035) were associated with a lower perinatal complications rate. CONCLUSIONS Based on low certainty evidence from observational studies, perinatal complication rates are not increased after ACOTT compared to the general pregnant population except for pre-eclampsia. This could be due to chemotherapy exposure, underlying medical conditions, and the common use of ART. Further larger studies are needed to explore the causes of increased pre-eclampsia incidence with ACOTT pregnancies.