Retrospective analysis of treatments with recombinant FSH and recombinant LH versus human menopausal gonadotropin in women with reduced ovarian reserve.

PURPOSES: The aim of this study is to determine whether a clinical advantage is gained with use of LH in combination with FSH or as a component of human menopausal gonadotropin (hMG) to achieve optimal ovarian stimulation. METHODS: In this study, we compared retrospectively two regimens, r-FSH/r-LH and hMG, for the treatment of women with reduced ovarian reserve, identified as subjects with antral follicle count (AFC) < 11 and AMH ≤ 1.1 ng/ml. RESULTS: Overall, the clinical pregnancy per started cycle was higher in the r-FSH/r-LH group (12.5 vs. 8.1%, P < 0.02), while implantation (11.1 vs. 9.5%) and miscarriage rates (29.9 vs. 35.9%) were comparable. Data were further analysed performing separate comparisons in subpopulations with different ranges of AFC, i.e. < 4, 4-6 and 7-10. Major differences between the two regimens were observed in women with AFC < 4. In this subpopulation, not only was the clinical pregnancies per started cycle higher in the r-FSH/r-LH group (10.2 vs. 1.5%, P < 0.01), but also implantation was significantly higher (13.0 vs. 2.8%, P < 0.02). CONCLUSIONS: A r-FSH/r-LH regimen appears to be beneficial for the treatment of women with extremely poor ovarian reserve. It should be considered however that, being retrospective, this study is affected by obvious limitations, such as post-treatment patient selection criteria and absence of randomisation.

Comparison of the obstetric and perinatal outcomes of children conceived from in vitro or in vivo matured oocytes in in vitro maturation treatments with births from conventional ICSI cycles.

STUDY QUESTION: Are the obstetric and perinatal outcomes of deliveries following in vitro maturation (IVM) cycles different from births generated from controlled ovarian stimulation (COS) cycles? SUMMARY ANSWER: The obstetric and perinatal outcomes of births from IVM cycles are comparable with those of ICSI treatments, including the incidence of major and minor abnormalities. WHAT IS KNOWN ALREADY: Only few and numerically small reports on the health of IVM children are currently available. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study involving 196 babies born from IVM cycles carried out with different priming regimens. Of these children, 79 developed from oocytes matured in vitro after 30 h of culture, while 104 originated from oocytes found mature and inseminated on the day of recovery. Thirteen babies were obtained from embryos developed from both types of oocytes. Data of these births were compared with those of 194 children born from COS ICSI cycles performed during the same period (March 2004 to December 2011). PARTICIPANTS/MATERIALS, SETTING AND METHODS: IVM cycles were done in the absence of gonadotrophin administration or with FSH and/or HCG priming. All oocytes were inseminated by microinjection. ICSI and ICSI cycles were chosen as a control group to exclude possible influences of the insemination technique. Couples in which maternal age was >39 years or affected by azoospermia were excluded to rule out major parental effects. MAIN RESULTS AND THE ROLE OF CHANCE: In single births, gestational age at delivery was comparable, but birthweight was significantly higher (P = 0.009) in children from IVM cycles (3091 ± 669 versus 3269 ± 619 g). In a separate analysis of the IVM group, comparing singleton births derived with certainty from oocytes matured in vitro (n = 71) or in vivo (n = 74), no statistically significant differences were observed in terms of birthweight (3311 ± 637 versus 3194 ± 574 g, respectively) and gestational age (38.9 ± 2.4 versus 38.4 ± 2.1 weeks, respectively). In twin births, gestational age was lower in IVM cycles, while weight at birth was comparable (ICSI, 2432 ± 540 g; IVM, 2311 ± 577 g). In single births, major and minor abnormalities were 2 (1.4%) and 6 (4.1%) in the ICSI group and 0 (0.0%) and 8 (5.2%) in the IVM category, respectively. In twin children, major and minor abnormalities were 1 (2.2%) and 2 (4.3%) in ICSI babies and 0 (0.0%) and 2 (4.6%) in IVM cycles, respectively. LIMITATIONS AND REASONS FOR CAUTION: The study is the largest conducted so far. Nevertheless, it is limited by its retrospective nature and the fact that most births of IVM treatments derived from oocytes found mature at recovery in cycles primed with HCG. A more comprehensive appraisal of the health status of IVM children will demand larger prospective studies. WIDER IMPLICATIONS OF THE FINDINGS: The study is consistent with previous reports suggesting a possible role of standard ovarian stimulation in determining a reduced birthweight in children born from COS cycles. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought to support this work. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation.

Cleavage kinetics of human embryos is indicative of ability to develop to blastocyst and implant. Recent advances in time-lapse microscopy have opened new and important research opportunities. In this study involving infertile couples requiring standard IVF/intracytoplasmic sperm injection treatment, zygotes were cultured by integrated embryo-culture time-lapse microscopy to analyse cleavage times from the 2- to the 8-cell stages in relation to the ability to develop to blastocyst, expand and implant. In comparison to embryos arresting after 8-cell stage, times of cleavage to 7- and 8-cell stages of embryos developing to blastocyst were shorter (56.5 ± 8.1 versus 58.8 ± 10.4h, P=0.03 and 61.0 ± 9.4 versus 65.2 ± 13.0 h, P=0.0008, respectively). In embryos developing to blastocyst, absence of blastocoele expansion on day 5 was associated with progressive cleavage delay. Implanting embryos developed to 8-cell stage in a shorter period compared with those unable to implant (54.9 ± 5.2 and 58.0 ± 7.2h, respectively, P=0.035). In conclusion, cleavage from 2- to 8-cell stage occurs progressively earlier in embryos with the ability to develop to blastocyst, expand and implant. Conventional observation times on days 2 and 3 are inappropriate for accurate embryo evaluation. The speed at which human embryos cleave is known to be suggestive of their ability to develop in vitro to the blastocyst stage and implant after transfer into the uterus. Recent advances in time-lapse microscopy, which allows acquisition of images every 15-20 min, have opened new and important research opportunities. In a retrospective study involving infertile couples requiring standard IVF or intracytoplasmic sperm injection treatment, fertilized oocytes were cultured by an integrated embryo-culture time-lapse microscopy system in order to perform an analysis of cleavage times from the 2- to the 8-cell stage in relation to the ability to develop to blastocyst, expand and implant. In comparison to embryos arresting after the 8-cell stage, times of cleavage to the 7- and 8-cell stage of embryos that developed to blastocyst were significantly shorter (56.5 ± 8.1h versus 58.8 ± 10.4h and 61.0 ± 9.4h versus 65.2 ± 13.0 h, respectively). In embryos developing to the blastocyst stage, absence of blastocoele expansion on day 5 was associated with a progressive cleavage delay. Implanting embryos developed to the 8-cell stage in a shorter period compared to those unable to implant (54.9 ± 5.2h and 58.0 ± 7.2h, respectively, P=0.035). In conclusion, cleavage from the 2- to the 8-cell stage occurs progressively earlier in embryos with the ability to develop to blastocyst, expand and implant. Conventional observation times on day 2 and 3 are appropriate for accurate embryo evaluation.

Anti-mullerian hormone as a predictive marker for the selection of women for oocyte in vitro maturation treatment.

PURPOSE: In oocyte in-vitro maturation (IVM) treatments, the chances to achieve a pregnancy are critically dependent on the retrieval of a suitable number of oocytes. In this study, we assessed the ability of circulating levels of anti-mullerian hormone (AMH) to identify normo-ovulatory women suitable for IVM treatment on the basis of the number of retrieved oocytes. METHOD: Serum AMH was quantified in normo-ovulatory women younger than 39 years undergoing IVM treatment. After immature oocyte retrieval and IVM, maximum 3 mature oocytes were used for treatment and all resulting embryos were transferred, as established by law. From 177 cycles, 991 oocytes were recovered. Following IVM, 484 mature oocytes were obtained (50.1%). RESULTS: The overall pregnancy rate per embryo transfer was 16.6% (25/151) and the implantation rate was 10.9% (30/278). Linear regression and receiver operating characteristic (ROC) analyses were applied to identify independent variables and quantify a cut-off AMH value able to identify patients suitable for IVM treatment. An AMH value of 1.28 ng/ml was identified as a threshold for the prediction of the retrieval of at least 5 oocytes, with a sensitivity of 93.4% and a specificity of 33.8%. Positive and negative predictive values were 67.6% and 75.0%, respectively. CONCLUSIONS: AMH can be adopted to identify women candidate for an IVM treatment from whom a suitable number of oocytes may be retrieved. This is of crucial significance during a non-stimulated cycle, in order to prevent an insufficient oocyte collection and rescue the treatment by implementing a conventional controlled ovarian stimulation.

Outcome of cycles of oocyte in vitro maturation requiring testicular sperm extraction for nonobstructive azoospermia.

OBJECTIVE: To assess the applicability of oocyte IVM in case of nonobstructive azoospermia (NOA). DESIGN: Case series. SETTING: Private IVF unit. PATIENT(S): All male partners were affected by NOA. Twenty-one women (20 normo-ovulatory and 1 with polycystic ovary) underwent 27 IVM treatments. The outcome of controlled ovarian stimulation (COS) cycles in normo-ovulatory women whose partners were affected by NOA was assessed for comparison. INTERVENTION(S): Spermatozoa from testicular sperm extraction (TESE) samples were retrieved and cryopreserved before treatment. MAIN OUTCOME MEASURE(S): Rates of fertilization, pregnancy per cycle and transfer, and implantation. RESULT(S): Twenty-seven IVM-TESE cycles were carried out in 21 women. Fertilization rate was 64.4%. In compliance with national legislation, no more than three oocytes were inseminated in each cycle and all developing embryos were transferred. Six single clinical pregnancies were ascertained (22.2% and 27.3% pregnancy rates per cycle and per transfer, respectively). One pregnancy ended in abortion. The others developed to term and gave rise to five healthy babies. Sixty couples underwent standard COS-TESE treatment. Rates of fertilization, clinical pregnancy per cycle, implantation, and abortion were 64.6%, 20.0%, 11.3%, and 16.7%, respectively. Eleven babies were born from ten pregnancies. CONCLUSION(S): Oocyte IVM may represent an option in NOA cases.