P-360 Autologous cryopreserved ovarian tissue transplantation and perinatal outcomes: a systematic review with pooled analysis
Authors: Erden M , Uyanik E , Demeestere I , Oktay K  H 
Published: July 2024

Abstract

Study question
What are the perinatal outcomes and complication rates after autologous cryopreserved ovarian tissue transplantation (ACOTT)?

Summary answer
Perinatal outcomes and complication rates are similar to those observed in the general population, except for pre-eclampsia, which complicates 9.4% of pregnancies following ACOTT.

What is known already
Ovarian tissue cryopreservation (OTC) offers the unique benefit of allowing the storage of tens of thousands of primordial follicles at once. Because it does not require sexual maturity or ovarian stimulation, it remains the exclusive fertility preservation option for prepubertal girls and for women who cannot delay fertility-impairing cancer treatments. The first ACOTT with previously cryopreserved tissue was performed in 1999. Since then, &gt;700 women have undergone ACOTT globally, which resulted in &gt; 200 babies being born. However, there is limited data on the perinatal outcomes of babies born after ACOTT.

Study design, size, duration
This systematic review was conducted following PRISMA guidelines. The protocol was prospectively registered on PROSPERO (CRD42023469296). 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. The databases were searched using the following keywords and MeSH terms: ovarian cryopreservation, transplantation, pregnancy, live birth and delivery. No language or publication period restrictions were imposed.

Participants/materials, setting, methods
Studies reported a live birth following ACOTT were considered eligible. Transplantations addressing primary ovarian insufficiency were excluded. Perinatal outcomes and complications were assessed. Additionally, we evaluated whether these results were independently affected by variables such as age at OTC, chemotherapy before OTC, ACOTT site, and mode of conception. The risk of bias in the studies was assessed based on selection, ascertainment, causality, and reporting domains. All statistical analyses were performed using SPSS Statistics (v30.0).

Main results and the role of chance
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. The mean ages at OTC and ACOTT were 25.5 and 31.8 years, respectively. Most of these women were exposed to some chemotherapy before OTC (51%). Of 162 childbirths, 66.7% were naturally conceived, with the remaining 33.3% being achieved through ART. The birth weight of 88.5% of newborns were appropriate for gestational age, while 8.3% and 3.1% were small- and large-for-gestational-age, respectively. 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 (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome in 1.9%. Incidences of gestational diabetes mellitus and preterm premature rupture of membranes were found to be 3.8% for each condition. Neonatal complications were reported in 3 recipients with 4 newborns: arthrogryposis, congenital cataract, and diaphragmatic hernia in a twin. Finally, among the defined variables, not receiving chemotherapy before OTC (odds ratio:0.22, 95% CI:0.07-0.68, P-value:0.009) and spontaneous conception (odds ratio:0.29, 95% CI:0.09-0.91, P-value:0.034) were associated with lower perinatal complications.

Limitations, reasons for caution
The other potential risk factors for perinatal complications, such as obesity and pre-existing chronic diseases, were not reported and hence could not be accounted for analysis. Moreover, most studies did not provide long-term follow-up data on the infants and complications may be under-reported.

Wider implications of the findings
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 and the common utility of ART. Further larger studies are needed to confirm our findings and verify the causes of increased pre-eclampsia incidence with ACOTT pregnancies.

Trial registration number
Not applicable