Monozygotic twin rate among ART centers: a multicenter analysis of data from 18 Italian units.

PURPOSE: The risk of monozygotic twins (MZTs) is increased in couples undergoing assisted reproductive technology (ART) treatments. Several systematic reviews have investigated the possible determinants linked to ART, but results obtained have not been conclusive. The study aims to investigate whether the incidence of MZT differed among ART centers. METHODS: This is a multicenter retrospective cohort study using the Italian ART National Registry database and involving the centers reporting data from individual ART cycles from 2015 to 2019. To investigate the incidence of MZT, only single embryo transfer cycles were considered. Women who had sex-discordant deliveries were excluded. MZT rate was calculated as the number of multiple pregnancies (more than one gestational sac at first ultrasound) out of the total number of clinical pregnancies. A binomial distribution model was used to determine the 95% CI of the frequency of MZT. RESULTS: Eighteen centers were included, and they provided data on 10,433 pregnancies. The total number of MZT was 162, corresponding to an incidence of 1.5% (95% CI: 1.3-1.8%). The rate of MZT among centers varied between 0% (95% CI: 0.0-25.9%) and 3.2% (95% CI: 1.3-8.1%). All the 95% CIs included 1.5%, rejecting the hypothesis that the MZT rate may significantly differ among centers. CONCLUSIONS: The rate of MZT did not significantly vary among ART centers. Local factors are unlikely to explain the increased rate of MZT in ART pregnancies.

Fertilization rate as a novel indicator for cumulative live birth rate: a multicenter retrospective cohort study of 9,394 complete in vitro fertilization cycles.

OBJECTIVE: To appraise the fertilization rate as a predictive factor for cumulative live birth rate (CLBR). DESIGN: Multicenter retrospective cohort study. SETTING: Ten in vitro fertilization clinics, whose data were collected and processed by the assisted reproductive technology (ART) Italian National Registry. PATIENT(S): 7,968 couples undergoing 9,394 complete intracytoplasmic sperm injection cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome measure was the CLBR in association with the fertilization rate intervals (<65%-group 1; 65%-80%-group 2; and >80%-group 3). Further data stratification was performed on the basis of maternal age (<34, 35-38, and 39-42 years) and number of retrieved oocytes (5-7, 8-10, and > 10 oocytes). RESULT(S): The CLBR was progressively higher in relation to the fertilization rate in groups 1, 2, and 3 (20.1%, 34.7%, and 41.3%, respectively). The number of recovered oocytes, embryo number per cycle, and cumulative pregnancy rate followed the same trend. The decrease in CLBR with increasing maternal age was significantly correlated with the fertilization rate and CLBR in all 3 maternal age groups. Multivariate logistic regression analysis showed fertilization rate as a factor independently associated with CLBR. CONCLUSION(S): The present data indicated a positive association between the fertilization rate and the CLBR, suggesting the predictive clinical relevance of this parameter and its adoption as a key performance indicator.

GnRH agonists to sustain the luteal phase in antagonist IVF cycles: a randomized prospective trial.

BACKGROUND: The addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone. METHODS: The primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions. RESULTS: A total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reached p < 0,01. No increase of OHSS risk was observed. CONCLUSIONS: From this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).

Perfectionistic traits and importance given to parenthood are associated with infertility-related quality of life in a sample of infertile women with and without endometriosis.

OBJECTIVE: To assess quality of life and psychological differences between infertile women with endometriosis and without endometriosis. To investigate predictive role of perfectionism, mindful awareness and beliefs about parenthood to quality of life in a sample of women with fertility problems. METHODS: 43 infertile women (22 with endometriosis; 21 without endometriosis) who recurred to Assisted Reproductive Treatments (ARTs) in the last 12 months took part to this cross-sectional study. Sociodemographic and clinical data were collected by means of a structured ad hoc questionnaire. Fertility Quality of Life, Fertility Problem Inventory - Need of parenthood subscale, Obsessive Beliefs Questionnaire - Perfectionism subscale, and Cognitive and Affective Mindfulness Scale - Revised were used to assess target outcomes. RESULTS: Any difference in quality of life and psychological condition was found between infertile women with and without endometriosis. Importance given to parenthood (beta = -.60, p < .001) and perfectionism (beta = -.30, p < .05) predicted quality of life related to fertility issues, independently of group. CONCLUSIONS: Infertility might elicit self-discrepancy between real-self (i.e. being infertile) and ideal-self (being fertile), which in turn has a negative impact on quality of life. Conclusions about the role of psychologist in ART's team are discussed.

Ovulation induction and luteal support with GnRH agonist in patients at high risk for hyperstimulation syndrome.

The aim of this study was to compare GnRHa trigger and luteal addition of triptorelin to hCG trigger for final oocyte maturation in women at high risk for OHSS undergoing IVF. A total of 423 patients were divided in two groups both stimulated using antagonist short protocol. Gonadotropins 75-150 UI/day were started on day 2-5, GnRH antagonist was added when the lead follicle was >14 mm and the final trigger was obtained with hCG 250 µg or triptorelin 0.2 mg. The luteal phase was supported with progesterone alone in the hCG group, with progesterone plus triptorelin 0.1 every other day from embryo transfer in the triptorelin group. In the triptorelin group we did neither have to suspend any embryo transfer, nor we have any early clinical OHSS. In the control group, 13 patients were suspended due to symptomatic high risk for OHSS and two patients developed a clinically significant OHSS. No statistically significant difference was observed in terms of clinical and ongoing pregnancy rates and implantation rates. Our results indicate that a protocol including GnRHa as trigger and an intensive luteal phase supported with GnRHa is safer than a standard antagonist protocol using hCG as trigger. It displays similar results, therefore it can be used as the first choice in patients at high risk for OHSS.

Ovarian and adrenal androgens may be useful markers to predict oocyte competence and embryo development in older women.

The aim of this retrospective analysis was to evaluate the association between serum levels of various hormones and in vitro fertilization (IVF) parameters in poor responder patients. Serum levels of anti-Müllerian hormone (AMH), dehydroepiandrosterone sulfate (DHEAS), androstenedione and testosterone were measured before the start of IVF treatment cycle. We found that serum AMH and DHEAS levels were positively correlated with the number of mature oocytes, fertilized oocytes and developed embryos, both in pregnant and in non-pregnant patients. In contrast, we found a positive correlation between serum androstenedione levels and IVF parameters in pregnant, but not in non-pregnant patients. In this latter group, androstenedione levels were positively associated with the number of mature oocytes and were negatively correlated with the number of fertilized oocytes. No correlation was observed with developed embryos. Finally, we reported a negative correlation between serum levels of testosterone and IVF parameters in pregnant women whereas no correlation was observed in non-pregnant patients. Our results suggest that serum AMH and DHEAS could be predictive for oocyte retrieval and embryo development. Moreover, the positive correlation between serum androstenedione levels and IVF parameters in pregnant patients, together with the lack of a consistent correlation in non-pregnant women seem to identify androstenedione as a more predictive marker for pregnancy outcome than testosterone. In addition, in our analysis testosterone shows a negative correlation with IVF parameters.

DHEA supplementation positively affects spontaneous pregnancies in women with diminished ovarian function.

The aim of this article is to describe unexpected spontaneous pregnancies in poor responder patients with long-term infertility, when treated with dehydroepiandrosterone (DHEA) supplementation prior to in vitro fertilization (IVF). Our evaluation was carried out in two groups of women. The first group included 39 young women with <40 years, all treated with DHEA because of a previous poor response. The second group included 38 women over 40 years who received DHEA supplementation. Controls for latter group were 24 comparable women who had not been treated with DHEA before the first IVF cycle to evaluate the spontaneous pregnancy rate during preparation to IVF. Three tablets daily of 25 mg micronized DHEA were administered for at least 12 weeks before starting a long stimulation protocol for IVF. Surprisingly, spontaneous pregnancy rate significantly increased after DHEA treatment, allowing to achieve 10 spontaneous pregnancies and 9 spontaneous ongoing pregnancies among young poor responders. Pregnancy rate and ongoing pregnancy rate obtained before starting the IVF cycle were also significantly higher in older women treated with DHEA than in the control group: 21.05% and 13.15% and 4.1% and 0, respectively. Our results show that DHEA supplementation improves the ovarian function in poor responders and in women over 40 years, suggesting that this molecule alone can raise fecundity and fertility treatment success in women with poor prognosis for pregnancy.

Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial.

OBJECTIVE: To determine the effects of myo-inositol on oocyte quality in polycystic ovary syndrome (PCOS) patients undergoing intracytoplasmic sperm injection (ICSI) cycles. DESIGN: A prospective, controlled, randomized trial. SETTING: Assisted reproduction centers. PATIENT(S): Sixty infertile PCO patients undergoing ovulation induction for ICSI. INTERVENTION(S): All participants underwent standard long protocol. Starting on the day of GnRH administration, 30 participants received myo-inositol combined with folic acid (Inofolic) 2 g twice a day and 30 control women received folic acid alone, administrated continuously. MAIN OUTCOME MEASURE(S): Primary end points were number of morphologically mature oocytes retrieved, embryo quality, and pregnancy and implantation rates. Secondary end points were total number of days of FSH stimulation, total dose of gonadotropin administered, E(2) level on the day of hCG administration, fertilization rate per number of retrieved oocytes, embryo cleavage rate, live birth and miscarriage rates, cancellation rate, and incidence of moderate or severe ovarian hyperstimulation syndrome. RESULT(S): Total r-FSH units (1,958 +/- 695 vs. 2,383 +/- 578) and number of days of stimulation (11.4 +/- 0.9 vs. 12.4 +/- 1.4) were significantly reduced in the myo-inositol group. Furthermore, peak E(2) levels (2,232 +/- 510 vs. 2,713 +/- 595 pg/mL) at hCG administration were significantly lower in patients receiving myo-inositol. The mean number of oocytes retrieved did not differ in the two groups, whereas in the group cotreated with myo-inositol the mean number of germinal vesicles and degenerated oocytes was significantly reduced (1.0 +/- 0.9 vs. 1.6 +/- 1.0), with a trend for increased percentage of oocytes in metaphase II (0.82 +/- 0.11% vs. 0.75 +/- 0.15%). CONCLUSION(S): These data show that in patients with PCOS, treatment with myo-inositol and folic acid, but not folic acid alone, reduces germinal vesicles and degenerated oocytes at ovum pick-up without compromising total number of retrieved oocytes. This approach, reducing E(2) levels at hGC administration, could be adopted to decrease the risk of hyperstimulation in such patients.

Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction.

BACKGROUND: Polycystic ovary syndrome (PCOS) is often characterized by chronic oligo- or anovulation (usually manifested as oligo- or amenorrhea), and hyperandrogenism. In addition, 30-40% of PCOS women have impaired glucose tolerance, and a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) seems to be implicated in the pathogenesis of insulin resistance. PCOS patients are subfertile as a consequence of such ovulatory disorders and often need drugs, such as clomiphene citrate or follicle-stimulating hormone, for ovulation induction, which increases the risk of multiple pregnancy and ovarian hyperstimulation syndrome. We hypothesized that the administration of an isoform of inositol (myo-inositol), belonging to the vitamin B complex, would improve the insulin-receptor activity, restoring normal ovulatory function. MATERIALS AND METHODS: Twenty-five PCOS women of childbearing age with oligo- or amenorrhea were enrolled in the study. Ovulatory disorder due to PCOS was apparently the only cause of infertility; no tubal defect or deficiency of male semen parameters was found. Myo-inositol combined with folic acid (Inofolic) 2 g twice a day was administered continuously. During an observation period of 6 months, ovulatory activity was monitored with ultrasound scan and hormonal profile, and the numbers of spontaneous menstrual cycles and eventually pregnancies were assessed. RESULTS: Twenty-two out of the 25 (88%) patients restored at least one spontaneous menstrual cycle during treatment, of whom 18 (72%) maintained normal ovulatory activity during the follow-up period. A total of 10 singleton pregnancies (40% of patients) were obtained. Nine clinical pregnancies were assessed with fetal heart beat at ultrasound scan. Two pregnancies evolved in spontaneous abortion. CONCLUSION: Myo-inositol is a simple and safe treatment that is capable of restoring spontaneous ovarian activity and consequently fertility in most patients with PCOS. This therapy did not cause multiple pregnancy.

Natural cycle as first approach in aged patients with elevated follicle-stimulating hormone undergoing intracytoplasmic sperm injection: a pilot study.

BACKGROUND: Poor ovarian response to standard in vitro fertilization-embryo transfer (IVF-ET) protocols or different regimens of treatment, as consequence of a diminished ovarian reserve, correlates strictly with patient age, elevated follicle-stimulating hormone (FSH) and reduced antral follicle count. The aim of the present pilot study was to evaluate the outcome of patients with poor prognostic features undergoing IVF-ET with natural cycles as a first approach and not as a consequence of a previous failure treatment. MATERIALS AND METHODS: Eighteen aged patients (mean +/- standard deviation 40.2 +/- 0.7 years, range 37-43 years) with elevated serum FSH and reduced antral follicle count underwent intracytoplasmic sperm injection (ICSI) after spontaneous ovulation. RESULTS: A total of 26 natural cycles with ICSI were analyzed. Pregnancy was observed in three patients, of which two were ongoing as assessed by fetal heart beat at ultrasound scan performed 4-5 weeks after ET. CONCLUSION: The overall pregnancy rates achieved (11.5% per cycle, 20.0% per ET) are comparable with those of conventional IVF-ET in aged patients, and not impaired by a single embryo transferred. Better embryo quality, as a consequence of natural selection of oocytes, better endometrium receptivity and monthly repeatability of the procedure, can balance the relatively low chance to perform ET.

Pathologic findings in hysteroscopy before in vitro fertilization-embryo transfer (IVF-ET).

BACKGROUND: The aim of this study was to evaluate hysteroscopy routinely performed prior to in vitro fertilization-embryo transfer (IVF-ET). METHODS: We analyzed in a prospective study 300 patients who underwent hysteroscopy before the first IVF-ET cycle. We analyzed then in a retrospective manner 300 patients who did not perform hysteroscopy. RESULTS: One-hundred-and-eighty (60%) hysteroscopies were normal but 120 (40%) revealed an unsuspected intrauterine abnormality. We did not find statistically significant differences between patients with normal or abnormal hysteroscopy in any characteristic. We found a statistically significant difference in pregnancy rate between women who performed hysteroscopy before IVF-ET cycle and in women who did not perform it. CONCLUSIONS: Hysteroscopy, as a routine examination, should be performed before the first IVF-ET cycle in all patients.