Long-term adverse effects of cyclophosphamide on follicular growth and angiogenesis in mouse ovaries.

The adverse effects of the anti-cancer agent cyclophosphamide (CTX) on follicular growth and ovarian angiogenesis were investigated in mice. CTX treatment irreversibly induced a loss of follicles through apoptosis and decreased microvascularization of the corpora lutea and follicles in a dose-dependent manner. Our findings demonstrated that CTX adversely affected the ovaries indicating the need to support an awareness of fertility preservation before chemotherapy is initiated.

Women's age and embryo developmental speed accurately predict clinical pregnancy after single vitrified-warmed blastocyst transfer.

The aim of this study was to establish a simple, objective blastocyst grading system using women's age and embryo developmental speed to predict clinical pregnancy after single vitrified-warmed blastocyst transfer. A 6-year retrospective cohort study was conducted in a private infertility centre. A total of 7341 single vitrified-armed blastocyst transfer cycles were included, divided into those carried out between 2006 and 2011 (6046 cycles) and 2012 (1295 cycles).

Ovarian stimulation using human chorionic gonadotrophin impairs blastocyst implantation and decidualization by altering ovarian hormone levels and downstream signaling in mice.

Ovarian stimulation induced by follicle-stimulating hormone and human chorionic gonadotrophin (hCG) is commonly used in assisted reproductive technology to increase embryo production. However, recent clinical and animal studies have shown that ovarian stimulation disrupts endometrial function and embryo development and adversely affects pregnancy outcomes. How ovarian stimulation impairs pregnancy establishment and the precise mechanisms by which this stimulation reduces the chances of conception remain unclear.

Maternal age and initial β-hCG levels predict pregnancy outcome after single vitrified-warmed blastocyst transfer.

Purpose: We retrospectively examined a large cohort of females who underwent single blastocyst transfer to determine if initial β-human chorionic gonadotrophin (β-hCG) levels on day 7 after single vitrified-warmed blastocyst transfer (SVBT) could be used to predict pregnancy outcome.

Methods: The treatment cycles that gave rise to the early pregnancies included in this study were performed from 2004 to 2011 in a private infertility center. In SVBT cycles, embryos were transferred during a natural cycle or after endometrial preparation with exogenous estrogen and progesterone.

Microtubule assembly and in vitro development of bovine oocytes with increased intracellular glutathione level prior to vitrification and in vitro fertilization.

Although vitrification is a useful technique for preservation of bovine oocytes, the yield of blastocysts derived from the vitrified oocytes is still low. We have recently reported a new type of cryoinjury, multiple aster formation, by which pronuclear migration and development of vitrified-warmed and in vitro-fertilized bovine oocytes are impaired. The aim of the present study was to investigate the effect of glutathione (GSH) content of vitrified bovine oocytes on multiple aster formation and subsequent in vitro development.

The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function.

The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs).

Minimal ovarian stimulation combined with elective single embryo transfer policy: age-specific results of a large, single-centre, Japanese cohort.

Background: The two main complications associated with the use of assisted reproduction techniques, ovarian hyperstimulation syndrome and multiple pregnancies, could be eliminated by milder ovarian stimulation protocols and the increased use of a single embryo transfer (SET) policy. A retrospective, cohort study was performed in private infertility centre to evaluate the embryological and clinical results of a large exclusively SET program according to patient age (lower or equal 29, 30-34, 35-39, 40-44 and equal or higher 45 years).

Materials: A total of 7,244 infertile patients have undergone 20,244 cycles with a clomiphene-based minimal stimulation or natural cycle IVF protocol during 2008.

Short-term, low-dose, non-steroidal anti-inflammatory drug application diminishes premature ovulation in natural-cycle IVF.

A retrospective cohort study was conducted in a private infertility centre to evaluate the use of non-steroidal antiinflammatory drugs (NSAID) in natural-cycle IVF (nIVF) treatment. A total of 1865 first-rank nIVF cycles performed during 2009–2010 were evaluated. Low-dose, post-trigger NSAID was administered in a non-randomized way in cycles at higher ovulation risk where an imminent LH surge was detected on triggering day.

Histocompatible parthenogenetic embryonic stem cells as a potential source for regenerative medicine.

Parthenogenesis is the process by which an oocyte develops into an embryo without fertilization. Parthenogenetic activation can be performed at various stages of meiosis, yielding embryos with a distinct genetic pattern of homozygousity and heterozygousity. The heterozygousity pattern specific to parthenogenetic embryonic stem (pES) cells derived from such embryos, can be predicted using genome-wide single nucleotide polymorphism (SNP) analysis to determine whether extrusion of the first or second polar body is prohibited.

Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer.

Objective: To compare neonatal outcome between children born after vitrified versus fresh single-embryo transfer (SET).

Study Design: Retrospective, single-centre cohort study of 6623 delivered singletons following 29,944 single-embryo transfers. Patients underwent minimal ovarian stimulation/natural cycle IVF followed by SET of fresh or vitrified-warmed (using Cryotop, Kitazato) cleavage-stage embryos or blastocysts.

Prevention of mitochondrial disease inheritance by assisted reproductive technologies: prospects and challenges.

Background: Mitochondrial diseases are caused by the mutations in both nuclear and mitochondrial DNA (mtDNA) and the treatment options for patients who have mitochondrial disease are rather limited. Mitochondrial DNA is transmitted maternally and does not follow a Mendelian pattern of inheritance. Since reliable and predictable detection of mitochondrial disorders in embryos and oocytes is unattainable at present, an alternative approach to this problem has emerged as partial or complete replacement of mutated mtDNA with the wild-type mtDNA through embryo manipulations.

Blastocyst culture is associated with an elevated incidence of monozygotic twinning after single embryo transfer.

In a 7-year (2002-2008) retrospective study of a large IVF program based on minimal ovarian stimulation and single ET (47,841 single ETs), monozygotic twinning occurred in 1.01% of 14,956 clinical pregnancies. Blastocyst culture was associated with a significantly increased monozygotic twinning risk (adjusted odds ratio, 2.

Successful vitrification of bovine and human ovarian tissue.

Ovariectomy and ovarian tissue cryopreservation has the potential to preserve the natural fertility of cancer patients prior to sterilizing chemo- and radiotherapies. Ovarian tissue cryopreservation with the conventional slow-freezing method has yielded limited success, partly because of oocyte loss during freeze-thaw and subsequent transplant. Based on the high-efficiency vitrification Cryotop method, a practical vitrification procedure for murine, bovine and human ovarian tissue was developed.

Natural IVF cycles may be desirable for women with repeated failures by stimulated IVF cycles.

Purpose: Although many reports support stimulated in vitro fertilization, several patients do not respond to it well. Furthermore, stimulated treatment could be associated with reduced ovarian response. We describe three successful cases involving patients of advanced age from whom dominant follicles were retrieved during the natural cycle.

Minimal ovarian stimulation with clomiphene citrate: a large-scale retrospective study.

Enclomiphene, an isomeric component of clomiphene citrate, acts antagonistically to the oestradiol receptor at the hypothalamus level, inhibiting both negative and positive feedback, and resulting in the induction of ovarian stimulation and suppression of ovulation. The minimal ovarian stimulation protocol takes full advantage of these characteristics of clomiphene citrate. Administration of 50 mg clomiphene citrate is initiated on cycle day 3, and from day 8 patients receive 150 IU of FSH every other day.

Production of the first offspring from oocytes derived from fresh and cryopreserved pre-antral follicles of adult mice.

Although mammalian ovaries contain hundreds of thousands of pre-antral follicles, fewer than 1% of these reach maturity and ovulation. Obtaining immature eggs from the pre-antral follicles of ovarian tissue could increase the possibility of preserving fertility in women undergoing anti-cancer treatment, and in women who wish to delay pregnancy and child raising until they are older. This study reports the birth of 10 healthy mouse pups derived from oocytes obtained from pre-antral follicles after adult ovary tissue cryopreservation and allotransplantation.

Highly efficient vitrification for cryopreservation of human oocytes and embryos: the Cryotop method.

Vitrification is frequently referred to as a novel technology of cryopreservation in embryology, although some young embryologists were born after its first successful application. Unfortunately, in spite of the accumulated evidence regarding its enormous potential value, most domestic animal and human laboratories use exclusively the traditional slow-rate freezing with its compromised efficiency and inconsistency. The purpose of this paper is to clarify terms and conditions, to summarize arguments supporting or disapproving the use of vitrification, and to outline its role among assisted reproductive technologies.

The efficacy and safety of managing ectopic pregnancies with transvaginal ultrasound-guided local injections of absolute ethanol.

Purpose: To describe the efficacy and safety of managing ectopic pregnancies (EP) with ultrasound-guided local injections of absolute ethanol (AE).

Methods: 69 cases of EP following IVF performed in our clinic were treated with a local injection of 0.3 ml AE with a 23-gauge needle under transvaginal ultrasonic guidance.

Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination.

Survival and development of human embryos was compared following slow cooling versus vitrification involving more than 13,000 vitrified embryos. In addition, the efficacy of an open system, the Cryotop, and a closed vitrification system, the CryoTip(trade mark), were compared using human blastocysts. One hundred percent of vitrified human pronuclear stage embryos survived and 52% developed to blastocysts as compared with 89% survival and 41% blastocyst development after slow cooling.

Growth and maturation of follicles and oocytes following xenotransplantation of porcine ovarian tissues and in vitro maturation.

This is the first report to show morphological evidence of in vitro maturation of oocytes recovered from xenotransplanted antral follicles. To develop a suitable tool for studing the growth and maturation of follicles and oocytes, we xenotransplanted small pieces of ovarian cortical tissue from sows, which contained small preantral follicles (primordial, primary, and secondary follicles; less than 0.05, 0.

Highly efficient vitrification method for cryopreservation of human oocytes.

Two experiments were performed to develop a method to cryopreserve MII human oocytes. In the first experiment, three vitrification methods were compared using bovine MII oocytes with regard to their developmental competence after cryopreservation: (i) vitrification within 0.25-ml plastic straws followed by in-straw dilution after warming (ISD method); (ii) vitrification in open-pulled straws (OPS method); and (iii) vitrification in <0.