Can an embryo re-biopsy for a previous inconclusive result influence clinical pregnancy compared to a successful PGT-M diagnosis from the first biopsy? The embryo re-biopsy intervention for PGT-M seems to reduce the implantation potential of a blastocyst. PGT-M allows embryo genetic profiling prior to transfer in couples with hereditary genetic disorders, as part of in vitro fertilization process. The need of a trophectoderm biopsy for the retrieval of a fragment of about 8-10 blastomeres is generally sufficient for optimal DNA amplification and molecular analysis. However, a proportion of embryos (approximately 10-12%) fails to be properly diagnosed after PGT-M testing due to inconclusive results. Therefore, as an attempt to obtain a genetic diagnosis, the embryo biopsy can be repeated on the same embryos although retesting involves a second round of biopsy and a second round of vitrification. Twenty-seven embryos from women undergoing PGT-M at an infertility center and transferred after two biopsies for genetic analysis were matched for age, fertility status, and study period, to embryos transferred after a conclusive PGT-M result after the first biopsy. The main outcome was the clinical pregnancy rate following embryo transfers in cases in whom embryos had a single biopsy, and when a re-biopsy was performed. The secondary outcome was the live birth rate. Ovarian stimulation, oocyte collection and fertilization were performed according to standard protocols. Embryos were cultured to blastocyst stage in groups of up to five, using one-step media. Blastocysts were biopsied on day 5, 6, or 7, employing either the pulling or flicking method based on their appearance. Biopsied cells were stored at -20 °C for genetic analysis. Vitrification was performed using Kitazato protocol. If results were inconclusive, a second biopsy was performed in surviving blastocysts. The median [interquartile range] number of retrieved and injected oocytes was similar between the two groups, as well as fertilization rate and number of blastocysts obtained. No difference between the two groups was also observed pertaining to the day of embryo culture in which the first biopsy was performed. Conversely, the number of non-diagnosticated and transferable blastocysts was lower in patients whose blastocysts were re-biopsied. In 90% of the re-biopsies an informative result was obtained. Clinical pregnancy rate was 52% (95% CI: 34-69) following the transfer of a single-biopsy blastocyst and 30% (95% CI: 16-48) following the transfer of a re-biopsied blastocyst. The likelihood to have a healthy baby was 33% (95% CI: 19-52) following the transfer of a blastocyst biopsied once and 22% (95% CI: 11-41) following the transfer of a re-biopsied blastocyst. The matching design, which aligns women’s age and fertility status in the two groups, allowed the assessment of pregnancy rates while avoiding potential confounding factors associated with retrospective analysis. Given that it is the first study with this design, a larger sample size is necessary to further elucidate these findings. Despite the limited sample size, these results are of extreme clinical relevance. They offer valuable insights for guiding decisions about embryos with unclear results, contributing to the improvement of strategies for selecting those with the highest probability of pregnancy. not applicable

Abstract Study question What is the compliance level of overweight/obese infertile patients to VLCKD? Is therapeutic adherence associated with weight loss and increased pregnancy rates? Summary answer Compliance level to VLCKD was surprisingly high. Participants experienced weight loss and pregnancy rates improved. What is known already Obesity and overweight are associated with infertility. They can adversely affect the hypothalamic-pituitary-gonadal axis, compromise oocyte quality and reduce endometrial receptivity. In addition, obesity exposes women at increased risk of obstetric complications. Although not always consistent, some evidence suggests a beneficial effect of diet in this setting, both for natural conception and in the context of ART. However, these studies also show low compliance, with many patients failing to lose enough weight to be clinically significant. VLCKD is a more aggressive approach to treating severe obesity and may represent a more effective option for these patients. Study design, size, duration This case-series prospective study has been performed at Unit of Obesity and Occupational medicine, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico Milano between May 2019 and September 2023 and involved 42 infertile women aged ≤ 40 years, affected by overweight-obesity (BMI 27.5-35), but without other relevant systemic pathologies. Participants/materials, setting, methods Treatment firstly included 3 months of VLCKD followed by 12 months of Low-Calorie Diet (LCD). The occurrence of any natural pregnancy led to the discontinuation of treatment. These cases were counted as successes. Throughout the study period, patients underwent regular dietary and anthropometric evaluations. Main results and the role of chance Of the 42 recruited patients, 36 adhered to the VLCKD. The median treatment duration was 5.5 months [Interquartile Range (IQR) 3-9]. The compliance rate was 86% (95% CI: 72-93%). A significant reduction in BMI was observed: at recruitment, patients had a median BMI of 36.6 [IQR 33.4-39.9], and at the end, it was 29.5 [IQR 27.3-32.7], with a weight loss of 19.9 kg [IQR 12.7-24.4]. Regarding pregnancy, 8 women (22%) achieved a natural pregnancy, while of the remaining 28 patients, 25 underwent ART treatments. Among these, 16 achieved pregnancy (13 by homologous cycles, two donor cycles, and one with ovulation induction). In total, 24 women achieved pregnancy. The intention-to-treat success rate was 57% (95% CI: 42-71%), and the protocol success rate was 67% (95% CI: 50-80%). Limitations, reasons for caution The case-series study design, by definition, does not require a control group and this could be considered a “weakness”. However, it should be noted that patients were likely to be highly motivated to lose weight and health-conscious, thus creating a sample group with distinctive characteristics. Wider implications of the findings The use of VLCKD in obese infertile women allows high compliance to be achieved. The probability of pregnancy also appears very promising. VLCKD could be considered as a first approach for the treatment of obese women who do not have contraindications to ketosis. Trial registration number not applicable

Abstract Study question Can sonohysterography-detected CSD have a deleterious effect on reproductive outcomes in women with secondary infertility undergoing IVF? Summary answer A 68% prevalence of CSD has been estimated in the study population. CSD significantly reduces the ongoing pregnancy rates in women undergoing IVF cycles. What is known already here is limited and conflicting evidence about the relation between Caesarean section, CSD and IVF treatment outcomes. Notably, most of the previous studies did not investigate the presence of CSD in infertile women with a history of Caesarian delivery. Furthermore, even if considered, the diagnosis of CSD is commonly based on transvaginal ultrasound assessment. Given the lower sensitivity of this method compared to saline infusion sonohysterography, an underestimation of the real effect is plausible. Study design, size, duration Retrospective cohort study of 122 women with a history of Caesarean delivery and an indication to IVF for secondary infertility referred to an Italian public assisted reproductive centre between 1 January 2016 and 30 April 2021. Participants/materials, setting, methods Women aged 18-43 with secondary infertility and a history of Caesarean delivery, tested for CSD with a saline infusion sonohysterography were included. Women with congenital uterine anomalies, intra-cavitary uterine pathologies, adenomyosis or previous myomectomy were excluded. CSD was defined as an anechoic indentation on the cesarean scar at the midsagittal plane, with a depth ≥ 2 mm. Main results and the role of chance Among the 122 women included, 83 (68%) were diagnosed with CSD by saline infusion sonohysterography. One hundred and fourteen patients underwent at least one IVF cycle: 76 (case group) had a CSD, 38 (control group) had a normal Caesarean scar. Groups were similar in patients and treatment characteristics. Clinical pregnancy rate was 43% in the CSD group and 71% in the control group (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.14-0.72; p = .006). Ongoing pregnancy rates were 33% and 58%, respectively (OR, 0.34; 95% CI, 0.15-0.76; p = .015). Similar results were obtained after adjusting for potential confounders on the regression analysis. Ectopic pregnancy and miscarriage rate along with obstetric and neonatal complications were similar in both groups. In a subgroup-analysis comparing women with CSD who achieved pregnancy and those who did not, pregnant patients had a greater residual myometrial thickness compared to those who did not get pregnant, even if this finding did not reach statistical significance (5.3 mm versus 4.4 mm, p .07). Limitations, reasons for caution Retrospective nature of the study does not permit to infer a causal association between CSD and the reduced chance of pregnancy. Our results are representative of an infertile population but generalization needs further investigation. The sample size was too small to reveal the potential effect on obstetric and neonatal outcomes. Wider implications of the findings In infertile patients with a previous Caesarean section, the presence of CSD is more common than previously thought. The presence of CSD might significantly reduce the IVF success rate. This finding is important in relation to the rising of Caesarean section rates and the possible application of CSD surgical repair. Trial registration number not applicable

Introduction Preimplantation genetic testing (PGT) is a significant challenge and a widely established reproductive alternative for couples with high-risk of transmitting an inherited monogenic disorder. In this study, we report single centre PGT experience at the Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico of Milan, Italy, from 2015 to 2018 after the ruling of the Italian Constitutional Court (96/2015) which legalized embryo genetic analysis in couples with high genetic risk for the first time in Italy. Four diseases were firstly considered: cystic fibrosis and beta-thalassaemia, as autosomal recessive disorders, and hemophilia A and B, as X-linked disorders. Material & methods Pre-clinical PGT workup was performed for 124 couples after genetic counselling. Thirty-one underwent PGD cycles for cystic fibrosis, 41 for beta-thalassemia and 3 couples for hemophilia A and 1 for hemophilia B. In vitro fertilization (IVF) procedures were used to generate embryos in vitro by intracytoplasmic sperm injection (ICSI). Blastocysts at day 5-7 were biopsied and vitrified post biopsy. Informative short tandem repeat (STR) markers were used for linkage analysis alone or in combination with family gene mutation detection by multiplex PCR. Following diagnosis, embryos with no gene mutation were transferred. Results Two hundred and forty-seven embryos were obtained. Blastocyst biopsy was performed on 236 day 5-7 embryos. Successful genetic results were obtained in 195 embryos (83%), 121 of those were diagnosed unaffected (62%) and genetically transferable. No conclusive diagnosis was obtained for 41 biopsies and 15 embryos were rebiopsied. Transfer of 84 cryopreserved embryos resulted in 46 pregnancy with an implantation rate of 55% per embryo transfer (ET). Pregnancies result in 26 live births and 8 miscarriages. Thirty-six embryos still remain cryopreserved. Fourteen couples underwent prenatal diagnosis and results were consistent with PGT genetic analysis. Parameters such as allele drop-out, contamination and recombination were considered to evaluate diagnostic accuracy and reliability of genetic testing. Our data showed an allele drop-out rate of 5%, amplification failure of 10% and recombination rate of 6%. Conclusions Our four years’ experience on PGT demonstrates that couples with high risks of transmitting genetic mutations that cause severe medical conditions can really benefit from PGT technique, as it represents a robust reproductive option preventing abortion of an affected pregnancy with great suffering to the pair. Our PGT positive experience serves as an incentive for the use of this procedure in other genetic diseases in our centre.

OBJECTIVE: To assess the reliability of serum AMH, compared to other markers of ovarian reserve, in predicting ovarian response in a ample number of patients with an indication to an in vitro fertilization (IVF) program. DESIGN: Prospective analisys MATERIALS AND METHODS: 378 patients with an indication for an IVF program were enrolled in the study. In all patients basal AMH, follicular stimulating hormone (FSH) and antral follicle count (AFC) were measured before starting the cycle. For each of these parameters receiver operating characteristic (ROC) curves were calculated in order to find an optimal thresold for the discrimination between normal and very poor responders women (stopped patients because of less than 3 selected follicles after ovarian hyperstimulation). RESULTS: The mean serum AMH and FSH levels of very poor responders patients, were found to be significantly lower if compared with ones of the normal responders (0.7 ± 0.8 vs 2.5 ± 2.2, p < .0001 and 14.2 ± 6.3 vs 9 ± 4.2, p < .0001 respectively). Same results were found considering AFC (2.1 ± 1.4 vs 5.8 ± 3.5, p < .0001). No differences were found regarding age, and body mass index (BMI). As a single prognostic predictor of very poor response basal AMH appeared to have a good discriminative potential as expressed by an ROC-area under curve (AUC) of 0.85, with a sensitivity of 89% and a specificity of 61% considering a cut-off level of < 0.5, with a positive predictive value of 92% and a negative predictive value of 53%. The calculated AUC for AFC and FSH were respectively 0.87 and 0.78. CONCLUSIONS: AMH seems to be an important additional marker of ovarian response in patients candidate to an IVF program; its reliability as a single prognostic predictor seems to be comparable to the one of AFC, but with clear differences in term of reproducibility and semplicity being AMH a cycle independent simple blood test.

OBJECTIVE: To assess the additional value of AMH as a marker of ovarian response in an in vitro fertilization (IVF) program, for patients expected to be at high risk of impaired ovarian reserve. DESIGN: Prospective analysis. MATERIALS AND METHODS: Forty seven patients with high levels of serum FSH (at least two values ≥ 12 mUI/ml) and an indication for an IVF program, were enrolled in the study. In all patients basal AMH and antral follicle count (AFC) were measured before starting the cycle. For AMH alone and for AFC, cut-off values and receiver operating characteristic (ROC) curves were calculated in order to find an optimal threshold for the discrimination between women with poor (≤ 4 oocytes) and normal response (> 4 oocytes) and very poor responders (stopped patients with less than 3 selected follicles and /or no oocytes retrieved). RESULTS: The mean serum AMH levels of very poor responder patients, compared with ones of the rest of the population, were found to be lower (0.35 ± 0.36 vs 1.17 ± 0.85, p < .0001). No differences were found regarding age, basal FSH levels, body mass index (BMI) and the total amount of recombinant FSH (tot FSH) used for controlled ovarian hyperstimulation (COH). As a single prognostic predictor of very poor response basal AMH appeared to have a good discriminative potential as expressed by an ROC- area under curve (AUC) of 0.83, with a sensitivity of 87.5% and a specificity of 73.3% using a cut-off level of ≤ 0.41. Same results were found considering AFC as prognostic factor (ROC-AUC 0.83). Considering oocytes retrieval as outcome, serum AMH levels were found to be statistically significantly different between normal and poor responders patients (0.71 ± 0.73 vs 1.56 ± 0.81, p = 0.002). To detect normal responders (> 4 oocytes) AMH showed an ROC-AUC of 82.2, with a sensitivity of 90.9% and a specificity of 75% using a cut-off level ≥ 0.96. AFC showed an ROC-AUC of 84.9, with a sensitivity of 80% and specificity of 86% considering a cut-off level > 4. CONCLUSIONS: AMH seems to be an important additional marker to predict ovarian response in ART programs for patients with high levels of serum FSH, and for this reason expected to be at high risk of poor response. Similar results were found for ACF, but with clear differences in term of reproducibility and simplicity in performing these two evaluations, being AMH a simple blood test, corresponding to an objective value, not needing to be performed in a particular phase of the menstrual cycle.

BACKGROUND: During IVF or ICSI cycles, ovarian hyperstimulation syndrome (OHSS) is a major problem. The aim of this prospective, multicentre, comparative study (using historical controls) was to assess the efficacy of a GnRH antagonist protocol in preventing OHSS in selected patients who had experienced OHSS or had been at risk of OHSS in their previous IVF/ICSI attempt. METHODS AND RESULTS: Patients underwent a new cycle where the same gonadotrophin protocol was used [same dose of recombinant FSH (rFSH)] but a different protocol was used for pituitary desensitization: cetrorelix 0.25 mg multiple-dose antagonist instead of GnRH agonist long protocol. Cetrorelix 0.25 mg was administered daily, starting when the leading follicle reached a diameter of 14 mm. In other words, rFSH was administered in the new cycle according to the dosage and the step-up or step-down modalities used during the previous cycle, independently of ultrasound findings and serum estradiol (E-2) levels. Eighty-seven patients entered the study. Out of the 87 cycles involving GnRH agonists, 49 (56.3%) were cancelled and out of the 87 involving GnRH antagonists 28 (32.2%) were cancelled [McNemar's test; 95% confidence interval (CI) -35.8% to -11.2%; P < 0.001]. After GnRH agonist cycles, we recorded 24 cases of OHSS (18 moderate and six severe; 27.6%), whereas after the GnRH antagonist cycles there were 10 cases of OHSS (nine moderate and one severe; 11.5%) (95% CI-26.4% to -5.7%; P=0.006). There was a statistically significant reduction in the total number of follicles with a diameter > 10 mm (Wilcoxon's test; Z=6.1; P < 0.001) and of E-2 levels on the day of HCG administration (2538 versus 4322.4 pg/ml; P < 0.001) in the GnRH antagonist cycles versus GnRH agonist cycles. Twenty-nine patients had an embryo transfer in the first cycle (76.3% of oocyte retrievals) and 57 in the cycle using GnRH antagonist (96.6%). This 20.3% difference was also significant (Z-test; 95% CI 6.8-36.0%; P=0.003). After the antagonist cycles, 18 pregnancies (20.7 per initiated cycle; 31.6% per embryo transfer) were obtained. CONCLUSIONS: Although this study presents some limitations owing to the use of historical controls, our data show a favourable effect of GnRH antagonists in reducing the incidence of OHSS and the number of assisted fertilization cycles cancelled because of the risk of OHSS in high responder patients. As a consequence, GnRH antagonist plus gonadotrophin administration could also increase the percentage of oocyte retrievals and embryo transfers in this high risk group of patients.

The following have a negative impact on IUI outcome: duration of infertility age of the female partner history of pelvic inflammation presence of severe male factor(s). Nevertheless, the most important risk associated with IUI after ovarian stimulation is the incidence of multiple gestation that can be as high as 29% (Gleicher et al., 2000). This is why in the presence of more than three follicles it has been suggested the procedure should be stopped or the cycle converted to IVF, but despite this risk the method is still widely used. Milder ovarian stimulation methods have been recently introduced in order to reduce the risk of iatrogenic twin pregnancies.

Compared to GnRh agonist, GnRH antagonists in IVF/ICSI stimulation cycles appear to be associated with a lower risk of ovarian hyperstimulation syndrome (OHSS). In our study we compare the efficacy of GnRH antagonists with the standard long protocol of GnRH agonists in selected patients at high risk of OHSS in their previous attempt of IVF/ICSI. Prospective, multicentric, comparative study, conducted in three different Infertility Units. From January 2002 to December 2002 patients who were at risk of OHSS during their first IVF/ICSI cycle with a mid-luteal long GnRH agonist plus gonadotrophins stimulation protocol, were recruited. We considered as risk factors in the agonist plus gonadotrophin cycle the presence of oestradiol levels at hCG day greater than 4,000 pg/ml and/or the presence of more than twenty follicles greater than 10 mm in mean diameter and/or the development of moderate or severe OHSS. Patients were then stimulated using the same recombinant FSH dosage of previous agonist cycle but in a multiple dose antagonist protocol: 0.25 mg of Cetrorelix (Cetrotide, Serono, Switzerland) were administered daily starting when leader follicle reached a 14 mm diameter. Cycles with GnRH antagonist were then compared to the previous agonist cycles of the same patients. Data were analysed using paired analysis and 95% confidence intervals were calculated. Eighty-seven patients, mean age 32.3±3.5 were included in the study. Comparison of cycles outcome and characteristics, with statistical significance, is reported in table 1 and table 2. Thirteen pregnancies were obtained in 87 cycles with GnRH antagonist (22% per pick-up). GnRH antagonist was effective in stimulation of multiple ovulation for IVF/ICSI in patients at risk of OHSS. Despite the same dosage of rec-FSH, GnRH antagonist multiple dose protocol reduced percentage of OHSS and increased percentage of completed cycles when compared, in the same patients, to previous agonist cycles. The mechanism of this effect might be the reduced number of small follicles and estradiol level at hCG day compared to agonist cycles. A prospective randomized study is warranted to definitively clarify whether protocols with a GnRH antagonist should be considered as a first-line treatment in patients at high risk of OHSS.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

In consideration of the high rates of genetic abnormalities reported by different authors within infertile couples, a committee of representatives of the twelve major national scientific societies prepared and published, in 2002, the Guidelines for the appropriate use of genetic tests in infertile couples (Eur J Hum Genet, 2002). The Guidelines strongly recommend to perform a karyotype analysis in each couple candidates to any assisted reproduction technique (ART). Cohort study. Starting from January 2002, all couples with an indication to ART were prescribed to have a chromosome analysis for both partners. A total of 3322 karyotypes were prescribed. 1551 females and 1536 males (3087 individuals, 92.9%) candidates to ART procedures, performed the chromosome analysis; the remaining patients did not perform the test, because of the onset of spontaneous pregnancies or as a consequence of renouncing to perform the procedure. The treatments suggested were as follow: 383 Intrauterine Insemination (IUI), 401 in-vitro fertilization (IVF) and 877 intracytoplasmic sperm injection (ICSI), including 34 sperm retrieval from testis or epididymis. Chromosome analysis was carried out on cultured peripheral lymphocytes using standard techniques. The cost of one chromosome analysis in our country amounts to 242,22 €. A total of 42 aberrant karyotypes was diagnosed (1.4%; 95% CI 1.0–1.8), corresponding to a frequency of 1.2% (19/1551) for women and 1.5% (23/1536) for men. Thirty-one structural and 11 numerical anomalies were found. Results according to the different indications are reported in Table I. Each abnormal karyotype costs 17803,17 €. An unexpected low percentage of chromosomal abnormalities has been observed in a cohort of couples with an indication to ART procedures. These results are much lower than those previously reported (3.8%-13.0%). Taking into consideration high costs of genetic tests, appropriate cost-effectiveness analyses are warranted to evaluate the opportunity of routine use of a genetic screening in infertile couples candidate to ART.

BACKGROUND:The precise role of GnRH antagonists in the armamentarium of drugs for stimulation of ovulation associated with intrauterine insemination remains to be clarified. In this study, we have compared two different protocols employing GnRH antagonists in order to determine the lower effective dose of gonadotrophins to use.METHODS:Sixty-six couples with unexplained infertility or moderate male subfertility were recruited. Starting on day 3 of the cycle, 32 patients were randomized to receive 50 IU of recombinant FSH per day, whereas 34 were treated with 50 IU of recombinant FSH on alternate days. Women received the GnRH antagonist Ganirelix at a dose of 0.25 mg per day starting on the day in which a leading follicle > or =14 mm in mean diameter was visualized, until HCG administration. Insemination was performed 34 h after HCG injection.RESULTS:The regimen with daily recombinant FSH was associated with a lower rate of mono-ovulation (53.3% versus 78.8%, P=0.06) but also with a higher clinical pregnancy rate per initiated cycle (34.4% versus 5.9%, P=0.005).CONCLUSIONS:A protocol of recombinant FSH 50 IU daily and GnRH antagonist may represent an effective and safe regimen for ovulation induction associated with intrauterine insemination.

Objective: Multiple pregnancies represent a serious risk in ART procedures, especially in ovulation induction with and without intrauterine insemination (IUI). The aim of our study was to obtain monofollicular cycles and single pregnancies with a new milder method of ovarian stimulation, using low dose gonadotrophins and GnRH antagonist in IUI cycles. Design: Multicentric randomized clinical trial. Materials/Methods: Patients with at least two years of unexplained infertility or mild male factor were randomized in two groups: group A was treated with recombinant FSH (r-FSH) 50 IU daily (Puregon, Organon) starting from the third day of cycle; patients in group B received r-FSH 50 IU on alternate days. GnRH antagonist (Orgalutran, Organon) at the dose of 0,25 mg daily was started, in both groups, from mean follicle diameter of 13–14 mm at ultrasound. Daily serum E2 were obtained during GnRH antagonist therapy; in addition, serum LH and progesterone (P) were assessed in hCG day. No supplementation was given and serum E2 and P were dosed at +2, +4, +6, +8, +10 from hCG day. Results: A total of 47 patients were recruited. Thirty-six cycles in 36 patients were fully evaluable. Mean estradiol serum levels in each group showed a plateau on day one after GnRH antagonist administration, then had a normal increase. Twenty-one cycles were monofollicular (44,4% in group A and 72,2% in group B); no more than two leader follicles (≥16 mm in diameter) developed and in almost 80% of cases no follicles of 11–15 mm in diameter were present at hCG. Progesterone profile showed a normal ovulatory pattern in both groups. In the 36 completed cycles, pregnancy rate was 27,7%; with the daily FSH administration, group A patients had an unexpectedly high pregnancy rate (42%) compared to that registered in group B (10%)(p <0,05) (table). TableResults in 38 cyclesGroupP ≥ 8 ng/mlN. follicles ≥16 mmN. follicles ≥11 mmPregnancy12≥312≥3N. (PR)SingletonA18 (95)8 (44)10 (56)0 (0)4 (22)10 (56)4 (22)8 (42)†p < 0.058 (100)B18 (95)13 (72)5 (28)0 (0)9 (50)6 (33)3 (17)2 (10)2 (100)Numbers in brackets are percentages. P: Progesterone in mid-luteal phase. PR: Pregnancy Rate.† p < 0.05 Open table in a new tab Numbers in brackets are percentages. P: Progesterone in mid-luteal phase. PR: Pregnancy Rate. Conclusions: The daily low-dose gonadotrophin and GnRH antagonist regimen induced 58,3% monofollicular cycles and, most important, was constantly associated with singleton pregnancies. Pregnancy rate was significantly different for the two methods of stimulation, being the daily regimen more effective. GnRH antagonist had, nor in follicular neither in luteal phase, detrimental effect on the ovarian stimulation. The remarkably high pregnancy rate associated to monofollicular cycles, is probably related to the proper timing of IUI due to GnRH antagonist administration. Supported by: none.

The therapy of anovulatory infertility is not meant to obtain a pregnancy at any cost, but to restore an ovulation as physiological as possible. This involves the use of drugs and therapeutical protocols to obtain monofollicular cycles. Monofollicularity reduces the two main risks of induction of ovulation: ovarian hyperstimulation syndrome and multiple pregnancy. The aim of this study is a review of the Literature on ovulation induction and a comparison with the data of our Sterility Service. The importance of the question will be examined together with the most used ovulation induction drugs: clomiphene citrate, gonadotrophins and pulsatile GnRH. The parameters considered are: the number of follicles, single or multiple pregnancies and ovarian hyperstimulation. After a review about ovarian stimulation, the results of our Sterility Service are presented: 364 cycles of ovulation induction with clomiphene citrate, low-dose gonadotrophins or pulsatile GnRH were monitored; monofollicularity was obtained in 58,48% of ovulatory cycles. Differences between drugs will be described in the text. The therapy of anovulatory infertility aims to restore a physiological ovulation and to obtain a single pregnancy, not a pregnancy at any cost.

Objectives: There is no general agreement on the need of LH during GnRH agonist + gonadotropins ovarian stimulation in cycles of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Aim of this study was to evaluate if LH administration after the recruitment phase can ameliorate the outcome of the ovarian superovulation for IVF/ICSI treatment. Design: Randomized clinical trial. Materials and Methods: Patients who underwent their first attempt of IVF or ICSI for tubal or male factor were recruited. Only the first cycle for each patients was considered. The patients were <40 years old, their Body Mass Index was <25 kg/m2, and they showed no endometriosis, no polycystic ovaries, neither previous ovarian surgery. All the patients underwent a standard mid-luteal long protocol GnRH agonist + gonadotropins stimulation using triptorelin 0.1 mg s.c. daily (Decapeptyl 0.1, Ipsen, Signes, France). Three ampules of recombinant FSH (Gonal F 75 IU, Serono, Rome, Italy) were administered for 5 days after pituitary desensitization was achieved. The sixth day of treatment the patients were randomized to continue recombinant FSH treatment (Group A) or to be switched to human menopausal gonadotropin (hMG) treatment (Menogon 75 IU, Ferring, Berlin, Germany) at the same dosage (Group B). The length of stimulation, the number of follicles, the plasma value of estradiol, LH and FSH, the number of retrieved oocytes, their quality, the fertilization rate and the pregnancy rate were evaluated and compared between the two groups. Results: Thirty-two patients were recruited: 16 in group A (9 IVF and 7 ICSI) and 16 in group B (8 IVF and 8 ICSI). There were four cycles canceled in each group. Results of treatments are reported in the following table (mean±SD); no difference is statistically significant): Tabled 1Age (years)Day of hCGE2 plasma level at hCG (pg/ml)LH plasma level at hCG (UI/l)Ampules of FSH/hMGGroup A34.6 ± 2.612.2 ± 1.41378 ± 9061.8 ± 1.219.5 ± 6.5Group B33.8 ± 2.911.6 ± 1.51937 ± 7691.4 ± 0.417.0 ± 5.2 Open table in a new tab Tabled 1Total follicles >15 mmTotal oocytes retrievedFertilization rate (%)Total embryos transferredPregnancy rate per ET6.8 ± 3.17.6 ± 4.050.9%1.8 ± 0.911.1%8.2 ± 2.69.3 ± 4.662.7%1.9 ± 1.116.7% Open table in a new tab Conclusion: There was no difference between groups in the evaluated ovarian stimulation parameters. The cost for cycles was nevertheless smaller in hMG stimulated cycles due to the lower price per ampule of hMG.

Chronic anovulation is probably the major cause of human infertility and is essentially associated with four distinct endocrine conditions; hyperprolactinemic anovulation, hypogonadotrophic anovulation, normo-gonadotrophic anovulation and hypergonadotrophic anovulation. Hyperprolactinaemia and microprolactinoma are frequent findings in young women and excessive prolactin secretion impairs ovarian function causing anovulatory subfertility. Dopaminergic treatment restores ovarian function and shrinks prolacinoma. In these patients restoration of fertility with prolactin lowering drugs does not increase the incidence of multiple pregnancies or early pregnancy loss. In the vast majority of hyperprolactinemic women pregnancy is safe and could be beneficial. Cabergoline is the most effective and tolerated of the antiprolactinemic drugs. Hypogonadotrophic anovulation is frequently associated with acute or chronic emotional stress and in this case the patient should be counselled. Explanation and reassurance are the first important management steps. The use of pulsatile gonadotrophin-releasing hormone is the best strategy to induce fertility. Patients with normogonadotrophic anovulation are likely to have polycystic ovary. The most cost effective profertility treatment is the administration of an anti-oestrogen such as clomiphene or tamoxifen. The second choice therapy for patients with normogonadotrophic anovulation is ovarian stimulation with human gonadotrophin preparations. Low dose modifications give pregnancy rates lower than that with the traditional high-dose step-up protocol and intensive monitoring is required, but multiple pregnancies are less frequent. No treatment is available to enable women with hypergonadotrophic anovulation to conceive. Fertility in these patients can be promoted only by an egg donation programme.