Maturation, embryo development and clinical outcomes in ICSI treatment cycles with completely immature oocytes at the removal of cumulus cells

Abstract

It has been reported that in-vitro matured oocytes have lower developmental potential than in-vivo matured oocytes. Usually embryos derived from in-vitro matured oocytes are de-prioritized for transfer. Occasionally combined transfer of embryos derived from in-vitro and in-vivo oocytes is performed if there are not enough embryos from in-vivo matured oocytes for an appropriate ET. It is hard to tell if embryos derived from in-vitro matured oocytes attribute to pregnancies or live births under this situation. Few data is available about the full term development of these embryos that are derived from superovulated immature oocytes. In this study we retrospectively analyzed the clinical outcome of ICSI treatment cycles containing only embryos derived from in-vitro matured metaphase II (MII) and metaphase I (MI) oocytes. Retrospective chart review from January 2001 to March 2004. All the cycles included in this study contained no mature oocytes at the removal of cumulus cells. A total of 139 immature oocytes from 38 ICSI treatment cycles were included in the study. Among them 94 were at MI and the other 45 at germinal vesicle (GV) stage. These oocytes were cultured in 5% O2, 5% CO2 and 90% N2 incubator for 4–6 hours prior to injection. Oocyte maturation was checked just prior to ICSI and recorded. All MI oocytes were subject to ICSI along with vitro-matured MII oocytes. Fertilization, embryo development and clinical outcome were recorded. Embryo transfer was performed in the morning of day 3. Remaining embryos after transfer were cultured to blastocyst for potential freezing as is standard in our practice. Among the 38 cases, 29, 6 and 3 cases fell within the range of 1–4 , 5–8, >8 oocytes retrieved respectively according to oocyte number. After 4–6 hours culture in vitro, 65 MII matured from 94 MI (69.1%) and 15 MI progressed from 45GV oocytes (33.3%). ICSI was not performed in 2 cycles because all oocytes remained at GV. In total, 109 MII/MI matured oocytes were injected. Fifty-one (47%) fertilized with 2PN and cleaved. The proportion of good quality embryos (8-cell stage with < or =20% fragmentation on day 3) was 37.3% (19/51). There was no embryo transfer in 16 ICSI cycles due to absolute fertilization failure. Thirty-eight embryos were transferred back to the uterus in the other 20 cycles, resulting in 2 singleton pregnancies. The implantation rate was 5.3%. Unfortunately both pregnancies resulted in spontaneous abortions. Six blastocysts were frozen on day 5 from 2 cycles. No pregnancy was obtained from one thawing tranfer cycle with 2 frozen blastocysts. Four frozen blastocysts remain in storage for later thawing. Although this is a small study, it can be concluded that embryo implantation and further developmental potential is heavily compromised after ICSI of superovulated, in vitro matured occytes. This limitation is most likely reflects an underlying patient or ovarian issue rather than with in vitro maturation itself. Patients should therefore be advised of the potential implications when this situation occurs.