Article
Successful pregnancy and delivery after ICSI with artificial oocyte activation by calcium ionophore in in-vitro matured oocytes: a case report

https://doi.org/10.1016/j.rbmo.2014.11.014Get rights and content

Abstract

The achievement of a successful pregnancy and delivery after oocyte activation with calcium ionophore is reported in a couple having low fertilization rates after intracytoplasmic sperm injection (ICSI) of in-vitro matured oocytes. A couple, in which the wife had polycystic ovary syndrome and the husband had moderate oligoteratozoospermia, showed a low fertilization rate in a previous in-vitro maturation cycle (2/11 [18.2%]). The most likely cause of complete fertilization failure or low fertilization rates is failure of oocyte activation. Therefore, artificial oocyte activation by calcium ionophore was combined with ICSI to achieve viable fertilized oocytes. Oocytes were stimulated with calcium ionophore for 30 min after ICSI. The fertilization rate of oocytes activated with calcium ionophore (13/15 [86.7%] and 7/9 [77.8%]) was higher than that of the non-activated oocytes. In the latest cycle, three embryos derived from the activated oocytes were transferred into the uterus on day 3. Subsequently, two gestational sacs were identified on ultrasound. The patient delivered dizygotic twins (girl 2260 g and boy 2760 g) at 35 weeks and 6 days gestation by caesarean section. This result suggests that calcium ionophore could be useful for oocyte fertilization in couples with low fertilization rates after ICSI of in-vitro matured oocytes.

Introduction

A number of disadvantages are associated with gonadotrophin use in ovarian stimulation for IVF cycles. These include the risk of ovarian hyperstimulation syndrome (OHSS) (Cobo et al., 1999), high drug costs, the need for daily injections and frequent monitoring. In-vitro maturation (IVM) of immature oocytes retrieved from unstimulated ovaries has the potential to avoid these problems. It has been reported that priming with human chorionic gonadotrophin (HCG) before immature oocyte retrieval in women with polycystic ovary syndrome improves the rate of oocyte maturation and pregnancy (Chian et al, 1999, Chian et al, 2000, Son et al, 2006), and, occasionally, results in obtainment of in-vivo matured oocytes at the time of retrieval (Son et al., 2008b).

Intracytoplasmic sperm injection (ICSI) is considered to be a powerful tool in assisted reproductive techniques. Although the fertilization rate with ICSI is typically considered to be the highest among the assisted reproductive techniques currently offered, the reported complete fertilization failure rate after ICSI ranges between 1.29% and 3% (Esfandiari et al, 2005, Liu et al, 1995). Complete fertilization failure or low fertilization rates after ICSI can be observed repeatedly in some couples. It is known that oocyte activation does not occur in about 70% of unfertilized oocytes after ICSI, despite accurate injection of the spermatozoon into the cytoplasm of the oocyte (Yanagida, 2004). The reasons for this occurrence may include failure of sperm head decondensation, premature sperm chromatin condensation, oocyte spindle defects and sperm aster defects (Swain and Pool, 2008). Furthermore, fertilization failure can occur as a result of limited availability of mature or morphologically normal oocytes, a lack of motile spermatozoa, and severe forms of teratozoospermia, such as globozoospermia (Dam et al, 2007, Yanagida, 2004). In women whose oocytes were not fertilized in previous IVF cycles, some methods of oocyte activation, such as electroporation (Mansour et al, 2009, Yanagida et al, 1999), or using chemical substances such as calcium ionophore (Ahmady, Michael, 2007, Borges et al, 2009, Chi et al, 2004, Eldar-Geva et al, 2003, Heindryckx et al, 2005, Kim et al, 2001, Kyono et al, 2009, Tejera et al, 2008, Terada et al, 2009, Tesarik, Sousa, 1995, Yoon et al, 2013), calcium ionophore and puromycin (Murase et al, 2004, Nakagawa et al, 2001), calcium chloride and ionophore (Rybouchkin et al., 1997), or ionomycin (Nasr-Esfahani et al., 2008), and strontium chloride (Kim et al, 2012, Kim et al, 2014) are reported to be effective in the formation of pronuclei and achieving childbirth. Specifically, calcium ionophore was found to be an excellent candidate for improving fertilization, embryo quality and pregnancy rates in women who showed complete fertilization failure or low fertilization rates (Chi et al, 2004, Eldar-Geva et al, 2003, Kyono et al, 2009, Terada et al, 2009, Tesarik, Sousa, 1995). Therefore, calcium ionophore is typically used clinically for artificial oocyte activation. To the best of knowledge, immature oocyte activation with calcium ionophore in the IVM cycle has not been reported.

In the present study, a case of successful pregnancy and delivery after artificial activation of IVM oocytes by calcium ionophore is reported.

Section snippets

Case report

A 32-year-old woman and her 33-year-old husband visited our clinic for primary infertility. The woman had irregular menstrual cycles and normal early follicular and mid-luteal phase serum hormone concentrations. A transvaginal ultrasound examination carried out during the early follicular phase established the diagnosis of polycystic ovary syndrome (PCOS). The diagnosis was based on Rotterdam consensus criteria (The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, 2004). Semen

Discussion

The benefits of IVF for several types of infertility has been proven, and ICSI has enabled fertilization of oocytes from patients whose partners have extremely low numbers of viable sperm and a very low probability of achieving fertilization in vitro. Complete fertilization failure or low fertilization rates, however, are still observed in some cases, such as those of globozoospermia, teratozoospermia, immotile spermatozoa, and even unexplained cases. Most fertilization failures after ICSI

Jun-Woo Kim is a senior clinical embryologist at Maria Fertility Hospital. He received his Medical Science Master's in Pharmacology from Inha University of Korea. He has over 10 years of experience in the field of clinical embryology. His current research interests include fertilization failure, oocyte activation and signalling, ICSI (PICSI and IMSI), cryopreservation (oocyte, cleavage, blastocyst and testicular spermatozoa), preimplantation genetic diagnosis or screening, mind-body medicine,

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