ArticleContribution of in-vitro maturation in ovarian stimulation cycles of poor-responder patients
Introduction
The first successful childbirth resulting from IVF was produced with a natural cycle of IVF following in-vitro maturation (IVM) (Steptoe and Edwards, 1978). The success rate of assisted reproduction technology, however, is strictly dependent on the number of oocytes and top-quality embryos obtained. Due to such limitation, the use of ovarian stimulation was developed, replacing the natural cycles of IVF (Johnston et al., 1981, Lopata et al., 1978).
During ovarian stimulation, women are usually treated with an agonist or antagonist of gonadotrophin-releasing hormone (GnRH) to block the action of the pituitary. In addition, ovarian stimulation using gonadotrophins is performed in order to induce the development and final maturation of multiple follicles (Eldar-Geva et al., 1999). After stimulation, due to a lack of perfect maturation synchronicity, oocytes of different developmental stages are retrieved (Cha and Chian, 1998, Trounson et al., 2001). In such cases, some immature oocytes, retrieved at either prophase I (PI) or metaphase I (MI) stages, have the potential to undergo nuclear maturation and further development (Magli et al., 2006). Thus, in-vitro nuclear maturation may be an alternative to increase the number of embryos obtained from ovarian stimulation cycles, especially in cases of poor-responder patients (Strassburger et al., 2004).
A dynamic assessment of the ovarian reserve could be associated with the ovarian response to stimulation with gonadotrophins during IVF treatment (Nikolaou et al., 2002). Previous studies suggest that, among patients undergoing IVF treatment, the prevalence of poor ovarian response is from 9% to 24% (Kumbak et al., 2009), which is defined based on the number of oocytes retrieved after ovarian stimulation.
Oocyte maturation remains a poorly understood process, generally defined as the period from the initiation of germinal vesicle breakdown to the completion of the nuclear changes leading to the extrusion of the first polar body (Lin and Hwang, 2006). The completion of the nuclear changes to produce a metaphase II (MII) oocyte does not, however, identify developmental competence and does not reflect the oocyte’s molecular and structural maturity (Trounson et al., 2001).
Previous studies reported successful fertilization, embryo development and pregnancy using immature human oocytes (Chian et al., 2004, Jaroudi et al., 1999, Lim et al., 2007, Papanikolaou et al., 2005). However, the performance of these oocytes is poor, resulting in reduced developmental potential (De Vos et al., 1999, Jaroudi et al., 1999).
Attempts have been made to promote maturation of immature human oocytes retrieved from stimulated cycles and, even though successful fertilization, embryo development and pregnancy have been reported (Chian et al., 2002, Kim et al., 2000, Liu et al., 2003), the literature on the developmental potential of these oocytes in ovarian stimulation cycles is still scarce.
The goal for this work was to investigate whether rescue spontaneous maturation (RSM) of immature oocytes retrieved from ovarian stimulation cycles of poor-responder patients, may improve the intracytoplasmic sperm injection (ICSI) outcomes. The primary endpoints of this trial were pregnancy and implantation rates. Secondary endpoints were the number of embryos available for transfer, cycle cancellation and miscarriage rates.
Section snippets
Experimental design
This cohort study included 440 poor-responder patients undergoing ICSI cycles, in which less than five MII oocytes and at least one immature oocyte (MI or PI oocyte) were retrieved after follicle aspiration. Written informed consent was obtained, in which patients agreed to share the outcomes of their cycles for research purposes. The study was approved by the local institutional review board.
Cycles were split into two groups based on the nuclear maturation status of the injected oocytes.
General characteristics
Experimental groups were similar for female age, number of aspirated follicles, number of MII retrieved oocytes, percentage of immature oocytes and total dose of FSH administered for ovarian stimulation, although the number of transferred embryos was higher in the RSM group (Table 1).
Nuclear maturation status and spontaneous in-vitro maturation
The overall number of retrieved oocytes was 1835. From these oocytes, 1345 (73.3%) were in MII stage, 227 (12.4%) were in MI stage, and 263 (14.3%) were in PI stage. Metaphase II stage was achieved in vitro in 271
Discussion
In stimulated cycles, pharmacological doses of gonadotrophins create a supraphysiological hormonal environment that induces the growth of a cohort of follicles, which, under natural conditions, would become atretic and regress (Fortune, 2001). De Vos et al. (1999) showed that ovarian stimulation leads to the retrieval of oocytes at various stages of meiotic maturity and that some of these oocytes may complete maturation spontaneously in vitro (Chian et al., 2002).
This study evaluated the
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Edson Borges Jr obtained his MD degree in 1984 at the University of Campinas, his first PhD in urology in 2005 at the Federal University of São Paulo and his second PhD in gynaecology in 2007 at the Botucatu Medical School in São Paulo State University. At present he is the founder partner and Managing Director of Fertility – Assisted Fertilization Center in São Paulo, Brazil and Scientific Director at Sapientiae Institute in São Paulo, Brazil.