Tony Tak Yu Chiu

Contribution of myo-inositol to reproduction.

Myo-inositol is involved in several aspects of human reproduction. Elevated concentrations of myo-inositol in human follicular fluids appear to play a positive function in follicular maturity and provide a marker of good quality oocytes. Nevertheless its positive role in PCOS women is a consequence of a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) that seems to be primarily implicated in the pathogenesis of insulin resistance. This article will review the involvement of inositol in female reproduction. After describing the biologic function of inositol and its derivatives, studies are quoted in which the role of inositol in fertility, oogenesis, and polycystic ovary syndrome are examined.

Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS.

In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).

Contribution of myo-inositol and melatonin to human reproduction

Diet is a critical factor for the development of both embryo and fetus, as well as maternal health. In particular, two natural molecules have been shown to exert beneficial effects on fertility, pregnancy wellness and embryo development: myo-inositol and melatonin, whose requirements increase during pregnancy. In the present review, we summarize the most important functions of melatonin and myo-inositol on male and female reproductive systems (oocyte quality and development, sperm quality), on the maintenance of a physiological pregnancy and on embryo development.

The rationale of the myo‐inositol and D‐chiro‐inositol combined treatment for polycystic ovary syndrome

PCOS is one of the most common endocrine disorders affecting women and it is characterized by a combination of hyper‐androgenism, chronic anovulation, and insulin resistance. While a significant progress has recently been made in the diagnosis for PCOS, the optimal infertility treatment remains to be determined. Two inositol isomers, myo‐inositol (MI) and D‐chiro‐inositol (DCI) have been proven to be effective in PCOS treatment, by improving insulin resistance, serum androgen levels and many features of the metabolic syndrome. However, DCI alone, mostly when it is administered at high dosage, negatively affects oocyte quality, whereas the association MI/DCI, in a combination reproducing the plasma physiological ratio (40:1), represents a promising alternative in achieving better clinical results, by counteracting PCOS at both systemic and ovary level.

A correlation of the outcome of clinical in vitro fertilization with the inositol content and embryotrophic properties of human serum.

PurposeThis study was designed to investigate whether the level of myo-inositol (MI) in human serum is critical for embryotrophic activity.MethodsThe embryotrophic properties of human serum were evaluated by the development of postimplantation mouse embryos [in vitro assay of Tam et al.(Fertil Steril48:834–839, 1987)].An enzymatic spectrophotometric method using myo-inositol dehydrogenase was used for determination of serum MI. The level of MI detected in serum was compared with the embryotrophic properties and the pregnancy outcome. The effect of MI on the embryotrophic activity of human serum was studied by supplementing the suboptimal serum samples that were unsupportive of embryo growth with extra MI.ResultsSerum obtained from patients having successful IVF pregnancies generally supported better development of postimplantation mouse embryos and contained higher levels of inositol, particularly if the serum sample was collected during the IVF treatment cycle. Serum samples obtained from patients with aborted pregnancies, though supporting mouse embryo development, contained significantly lower concentrations of inositol. An improvement of the embryotrophic properties with exogenous inositol supplement was achieved in some but not all of the suboptimal serum samples studied.ConclusionsIt is possible that other factors in addition to inositol are crucial in promoting better embryonic development.

Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in Obstetrics and Gynecology – assisted reproduction technology

Abstract A substantial body of research on mammalian gametogenesis and human reproduction has recently investigated the effect of myo-inositol (MyoIns) on oocyte and sperm cell quality, due to its possible application to medically assisted reproduction. With a growing number of both clinical and basic research papers, the meaning of several observations now needs to be interpreted under a solid and rigorous physiological framework. The 2013 Florence International Consensus Conference on Myo- and D-chiro-inositol in obstetrics and gynecology has answered a number of research questions concerning the use of the two stereoisomers in assisted reproductive technologies. Available clinical trials and studies on the physiological and pharmacological effects of these molecules have been surveyed. Specifically, the physiological involvement of MyoIns in oocyte maturation and sperm cell functions has been discussed, providing an answer to the following questions: (1) Are inositols physiologically involved in oocyte maturation? (2) Are inositols involved in the physiology of spermatozoa function? (3) Is treatment with inositols helpful within assisted reproduction technology cycles? (4) Are there any differences in clinical efficacy between MyoIns and D-chiro-inositol? The conclusions of this Conference, drawn depending on expert panel opinions and shared with all the participants, are summarized in this review paper.

Regulation of human oviductin mRNA expression in vivo.

OBJECTIVE To examine changes in oviductin mRNA expression in oviductal mucosal tissue from fertile women throughout an ovulatory cycle. DESIGN Semiquantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis of oviductin mRNA. SETTING University-based obstetrics and gynecology department. SUBJECT(S) Twenty women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids. INTERVENTION(S) The mucosal layer was isolated from the oviduct tissue, and semiquantitative RT-PCR was performed. MAIN OUTCOME MEASURE(S) The relationship between serum estradiol, luteinizing hormone, and progesterone concentrations and the expression of oviductin mRNA. RESULT(S) There was a significant positive correlation between serum estradiol and luteinizing hormone concentrations and oviductin mRNA expression. There was a significant inverse correlation between serum progesterone concentrations and oviductin mRNA expression. CONCLUSION(S) Little is known about the regulation of human oviductin. This study was the first to examine the relationship between oviductin mRNA expression and serum estradiol and luteinizing hormone and progesterone concentrations in fertile women. Estradiol and luteinizing hormone both have a stimulatory effect on oviductin mRNA in humans, however, it is difficult to determine whether the effects are independent of one another, as the luteinizing hormone surge is dependent on the estradiol increase. Progesterone shows a clear inhibitory effect on oviductin mRNA.

A correlative study on the embryotrophic property of patient’s serum and the outcome of in vitro fertilization of human oocytes

The embryotrophic property of patients serum previously used for in vitro fertilization (IVF) was studied by culturing postimplantation organogenesis-stage mouse embryos in a medium containing equal parts of Dulbeccos modified Eagles medium and the patients serum. Results of embryo culture experiments were generally found to correlate well with the outcome of IVF. Serum of patients whose oocytes were fertilized and developed to cleavage-stage embryos scored highest for embryotrophic parameters such as morphologic score and protein content of the mouse embryo. There was no significant difference in terms of serum embryotrophic activity between patients who became pregnant after embryo transfer and those who did not. When mouse embryos were cultured in serum from cycles with poor IVF results, i.e., oocytes failed to be fertilized or fertilized oocytes failed to cleave or cleave abnormally, significantly retarded embryonic growth and a higher incidence of malformed embryos were observed. However, in two cases where IVF failed as a result of poor semen quality, the patients serum was found to be supportive of mouse embryonic development.

Human oviductin mRNA expression is not maintained in oviduct mucosal cell culture

OBJECTIVE To determine whether oviduct mucosal cell culture supports the continued production of oviductin, a putative embryotrophic protein. DESIGN Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of oviductin messenger RNA (mRNA) expression after oviduct mucosal cell culture. SETTING University-based obstetrics and gynecology department. PATIENT(S) Ten women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids. INTERVENTION(S) The mucosal layer was isolated from the oviduct tissue and subjected to routine culture conditions; semiquantitative RT-PCR was performed. MAIN OUTCOME MEASURE(S) The relationship between duration of cell culture and expression of oviductin mRNA. RESULT(S) There was a significant reduction in oviductin mRNA expression after 3 days in culture, with a complete loss after 6 days in 70% of the samples and after 12 days in the remaining 30%. CONLCUSION(S): This is the first study to investigate whether oviductin mRNA continues to be expressed in cultured human oviduct mucosal cells. Our results suggest that oviduct mucosal cells lose their ability to produce oviductin after short-term culture. This method of culture does not appear to be appropriate for a coculture system reliant upon oviductal secretion of oviductin.

Localization of fucosyl glycoconjugates in human oocytes following insemination for in vitro fertilization

Human oocytes that failed to cleave after insemination were examined for the presence of fucosyl glycoconjugates in the perivitelline space by staining withUlex europeaus lectin conjugated to fluorescein isothiocynate. Oocytes that formed two or three pronuclei following first insemination always exhibited positive lectin staining similar to that observed with in vitro fertilized mouse oocytes. Among those oocytes that failed to form any pronuclei after the first insemination attempt, only 5% contained lectin positive substances in the perivitelline space. Upon reinsemination, a higher percentage of those oocytes produced lectin-positive materials, although pronuclei were still absent. The appearance of fucosyl glycoconjugates in these oocytes might be the result of the release of cortical granules triggered by sperm penetration or, more likely, due to spontaneous granule discharge in senescent oocytes.