Repeated superovulation induced changes in the oocytes, embryos and somatic cells

Infertility is one of the leading health problems in India as well as globally. With increased pollution and change in the life style, reproductive health of human beings is on the decline. A recent report suggests that about 15–20 million people in India are infertile. Intrauterine insemination (IUI) and assisted reproductive technology (ART) involving, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have become a ray of hope for millions of infertile couple. Ovulation induction and superovulation in infertile women is a common procedure before IUI or IVF/ICSI respectively. But despite advances in the past 3 decades, the success rate of IUI and IVF is limited by low success rates (~10-15% and 30-35% respectively) due to which most of the times infertile women have to undergo repeated ovulation induction or superovulation. Under these circumstances, microtrauma caused to the ovarian epithelium by repeated, uninterrupted ovulation and supraphysiological hormonal levels may increase the risk of cancer in hormone responsive organ such as ovary. Earlier studies reported in the literature and a recent work done in our laboratory have revealed significant changes in the oocyte quality, developmental potential of the embryos and increased genomic instability in somatic cells of Swiss albino mouse subjected to repeated superovulation. The preliminary study conducted in our laboratory has shown that the mouse oocytes subjected to repeated superovulation had significantly higher ROS level, increase in oocyte diameter with large perivitelline space and altered distribution pattern of mitochondria. The embryos derived from such oocytes had lower blastocyst rate and delay in cleavage rate (Personal observation). However, there is no information available in the literature to indicate whether these changes induced by repeated superovulation have any adverse effect on the progenies either at early developmental stage or at later stages. Apart from the reports available on its adverse effect on gametes and embryos, contradictory reports available in the literature suggesting the possible association between fertility drugs and cancer risk in infertile women have drawn attention of reproductive biologists and increased the anxiety in infertile couple. Few studies indicate a higher risk of breast cancer in women who have undergone ovulation induction for fertility treatment. Therefore, it is timely and of immense medical importance to assess the safety of ovulation induction and superovulation protocols and its possible effect on the cellular changes in the gametes and embryos derived from them. (Supported by Science and Engineering Research Board, Govt. of India)