Sandro Gerli

Use of fluorescence in situ hybridization to assess the chromosomal status of embryos obtained from cryopreserved oocytes.

OBJECTIVE To analyze the chromosomal status of human embryos obtained from frozen-thawed oocytes. DESIGN Fluorescence in situ hybridization analysis of embryos obtained after oocyte cryopreservation. SETTING Department of Obstetrics and Gynecology at the University of Perugia, Italy, and the Instituto Valenciano de Infertilidad, Spain. PATIENT(S) Oocyte donors (n = 43). Fertilization, development, and chromosomal status of the embryos were compared with a control group (n = 18) of patients undergoing preimplantation genetic diagnosis for sex chromosome-linked diseases. INTERVENTION(S) Collection of oocytes after conventional ovarian stimulation and cryopreservation using propanediol as the cryoprotectant and a slow freezing procedure. Microinjection of surviving metaphase II oocytes and evaluation of fertilization and embryo development up to blastocyst stage. Chromosomal analysis after embryo biopsy. MAIN OUTCOME MEASURE(S) Survival, fertilization, and blastocyst rates. Embryo chromosomal analysis employing specific probes for chromosomes 13,18,21, X and Y. RESULT(S) The overall survival rate was 59.4%. There was no difference between cryopreservation and control groups in fertilization rates (76.5% vs. 90.5%) or blastocyst development (29.6% vs. 35%). The percentage of blastocysts from the original number of cryopreserved oocytes was only 5.6%, comparable to the 5.9% obtained in the control group. The percentage of embryos with abnormal number of chromosomes in the cryopreservation group (28.6%) was comparable to the 26% observed in the controls. CONCLUSION(S) Fertilization and cleavage rates after oocyte freezing are acceptable. Survival is, however, still poor, leading to overall results that make the technique clinically inefficient. There is no increase in the rate of chromosomal abnormalities, indicating that the technique is, nevertheless, safe enough to be further explored and improved.

Progesterone and pregnancy.

Purpose of review Progesterone is an essential hormone in the process of reproduction. Although the pharmacokinetics and pharmacodynamics of progesterone have been well studied, its use in the pathophysiology of pregnancy remains controversial. One of these concerns is the way in which the hormone is administered. Recent findings In obstetrics the most frequent uses of progesterone are in the treatment of threatened abortion, prevention of recurrent miscarriage, or in the support of the luteal phase in assisted reproduction programmes, and in threatened preterm labour. Randomized, controlled trials showed that women who received progesterone were statistically significantly less likely to have recurrent miscarriages before 34 weeks, to have an infant with birth weight of 2.5 kg or lower, or to have an infant diagnosed with intraventricular haemorrhage. There is currently, however, insufficient information to allow recommendations regarding the optimal dose, route and timing of administration of progesterone supplementation. Summary Progesterone has shown to be efficacious when continuation of pregnancy is hampered by immunological factors, luteinic and neuroendocrine deficiencies and myometrial hypercontractility. This may explain the reduction in the incidence of preterm birth in high-risk pregnant women using high-dosage prophylactic progesterone.

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).

High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial.

Objective: To compare the effectiveness of clomiphene citrate (CC) alone or combined with phytoestrogens (PE) in ovulation induction in patients who had intrauterine insemination in a randomized, double-blind study. Methods: A total of 134 women aged 25-35 years, who were infertile for at least 2 years and who had oligomenorrhea or amenorrhea associated with a positive menstrual response to the intramuscular progesterone-challenge test were enrolled. They were randomly treated with CC (100 mg daily for 5 days) and CC (100 mg daily for 5 days) in combination with PE (1500 mg daily for 10 days). We estimated the difference in uterine artery pulsatily index, number of preovulatory follicles, endometrial thickness, and pregnancy rate. Results: Both treatments increased follicle-stimulating hormone, luteinizing hormone, and 17β-estradiol plasma concentrations, but the differences were not statistically significant. However, the differences in endometrial thickness of the two groups were statistically significant. No significant differences in the pulsatility index values and in the number of preovulatory follicles were noted. Conclusion: A high dose of phytoestrogens can reverse the deleterious effects of clomiphene citrate on endometrial thickness and could contribute to higher pregnancy rates.

Does cold loop hysteroscopic myomectomy reduce intrauterine adhesions? A retrospective study

OBJECTIVE To estimate the prevalence and the characteristics of intrauterine adhesions after cold loop resectoscopic myomectomy. DESIGN Retrospective study. SETTING Endoscopic gynecologic center. PATIENT(S) 688 women with one or more G1-G2 myomas. INTERVENTION(S) Cold loop resectoscopic myomectomy and diagnostic hysteroscopy in all patients 2 months after surgery. MAIN OUTCOME MEASURE(S) Integrity of the uterine cavity and prevalence of intrauterine synechiae. RESULT(S) A total of 806 myomas were removed, ranging from a minimum of one to a maximum of five fibroids removed for each surgical procedure. Complications were reported in eight cases (1.16%). No hemorrhage, intravasation clinical syndrome, or perforation with the thermal loop were registered. Synechiae were found in 29 patients (4.23%): in 2 patients a new surgical hysteroscopic treatment was required to remove fibrous synechiae, and in 27 patients light adhesions were removed with the tip of the instrument in outpatient hysteroscopy. Neither intrauterine device nor anti-adherence mixtures were used at the end of surgery. CONCLUSION(S) The cold loop hysteroscopic myomectomy is a safe and effective procedure that seems to be associated with a lower rate of intrauterine adhesions in comparison with the reported literature. The issue appears to be of notable importance for fertility patients.

The changing role of progesterone in preterm labour

Progesterone is an essential hormone in the process of reproduction. It is involved in the menstrual cycle, implantation and is essential for pregnancy maintenance. Although the pharmacokinetics and pharmacodynamics of progesterone have been well studied, and since 1935 it has been synthesised and is now available commercially, its use in the pathophysiology of pregnancy remains controversial. One of these concerns is the way in which the hormone is administered, with parenteral use proving the best way to obtain optimal plasma levels. Another concern is the paucity of randomised controlled trials and the different dosages and populations studied. As a result, the therapeutic application of progesterone in pregnancy is restricted to the prevention and treatment of threatened miscarriage, recurrent miscarriage and preterm birth. Progesterone is efficacious when continuation of pregnancy is hampered by immunological factors, luteinic and neuroendocrine deficiencies and myometrial hypercontractility. This may explain the reduction in the incidence of preterm birth in high risk pregnant women using high‐dosage prophylactic progesterone.

Pregnancy outcome in women aged 40 years or more

Objective: The study aimed to analyze the pregnancy outcome of women aged 40 years or more. Methods: A matched retrospective cohort study comparing women aged 40 years or more with a control group aged 20 to 30 years is described. Multivariate logistic regression models were fitted for the prediction of preterm birth and cesarean delivery. Results: Pregnancy-induced hypertension, preeclampsia and placenta previa were similar in both groups, but a higher rate of gestational diabetes was found in elderly patients (odds ratio [OR] 3.820, 95% confidence interval [CI] = 1.400–10.400; p < 0.0001). Preterm delivery was significantly more frequent in elderly women (OR 1.847, 95% CI = 1.123–3.037; p = 0.020). Gestational diabetes and pregnancy-induced hypertension were strongly associated with preterm delivery and advanced maternal age was not an independent risk factor for preterm delivery. The cesarean delivery rate was significantly higher in the study group (OR 3.234, 95% CI = 2.266–4.617; p < 0.0001). The variables most influencing the cesarean delivery rate were maternal age, analgesia, parity, premature rupture of the membranes and gestational hypertension. No significant differences were detected in neonatal birth weight and Apgar score. Conclusions: Patients aged 40 years or more have been demonstrated to carry a favorable pregnancy and neonatal outcome, similar to younger patients. The risk of cesarean delivery was higher in patients with advanced maternal age, in nulliparous and in women with a previous cesarean section. The risk of preterm delivery was not related to age but it was strongly associated with gestational diabetes and pregnancy-induced hypertension.

Early ultrasonographic diagnosis and laparoscopic treatment of abdominal pregnancy.

An early, pre-operative, ultrasonographic diagnosis of an abdominal pregnancy was made and successfully treated by laparoscopy in an asymptomatic woman with a 8-weeks abdominal pregnancy. The early, ultrasonographic diagnosis allowed an easy, mini-invasive, endoscopic treatment of the potentially life threatening pregnancy.

Low Dose of Ethinyl Estradiol Can Reverse the Antiestrogenic Effects of Clomiphene Citrate on Endometrium

Fifty healthy, voluntary patients aged between 20 and 30 years with regular menstruation and plasmatic progesterone level >10 ng/ml at the midluteal phase have been enrolled in this study. They were randomly treated with clomiphene citrate (CC; group A) or CC + ethinyl estradiol (0.05 mg group B, or 0.02 mg group C). We estimated the difference in uterine artery pulsatily index, endometrial thickness and histological dating and morphometric analysis of endometrium. No significant differences in Pulsatility Index values and in the number of preovulatory follicles were noted. The difference between endometrial thickness, histological dating and morphometric analysis of the endometrium were statistically different between groups B and C vs. A. Our study shows that CC has a deleterious effect on endometrium maturity and that adding ethinyl-E2 produces a favorable endometrial response even with very low doses.

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.