Search

Study question Does elevated late-follicular phase estrogen and progesterone levels have an impact on blastocyst utilization and/or cumulative live birth rates in freeze-all cycles? Summary answer High estrogen or progesterone on the day of ovulation trigger is associated with poor blastocyst utilization but comparable cumulative live birth rates in freeze-all cycles. What is known already Several studies suggest impaired clinical outcome in cycles with high estrogen (>3500 pg/ml) or progesterone (>1.5 ng/ml) levels. However, these data were derived from cycles where top-quality embryo(s) were transferred in the fresh cycle and surplus embryos were frozen. These findings might be confounded by alterations in endometrial receptivity. Freeze-all cycles might provide a better model to assess the impact of high late-follicular estrogen or progesterone levels on laboratory and clinical outcome. Study design, size, duration We performed a retrospective cohort study of all IVF cycles (n = 712) between 2016 and 2018 where the entire cohort of embryos was cryopreserved at the blastocyst stage. After excluding cases with Participants/materials, setting, methods Women were classified into four groups by the indication for freeze-all strategy as elevated progesterone (high P, n = 61), high estrogen (high E, n = 224), elective freezing (elective, n = 114) and tubal-endometrial pathologies (TEP, n = 60). The primary outcome was the cumulative live birth rate in subsequent thaw-transfer cycles and the secondary outcome was the blastocyst utilization rate. Groups were compared using ANOVA and Cox regression analyses to adjust for confounding variables. Main results and the role of chance The mean age of the study group was 32.8 ± 5.3 years, total number of oocytes and cryopreserved blastocysts were 15.0±7.6 and 4.2±3.0, respectively. The high-E group was younger (31.5 ± 5.2 years) and had higher peak E2 levels (4078.9 ± 588.4 pg/ml), number of oocytes (19.7 ± 7.0), cryopreserved embryos (5.3 ± 3.3) and transfer cycles (2.3 ± 1.4) than the other groups. Blastocyst utilization rate was significantly lower (40.4%) compared to elective freezing (53.6%) and TEP groups (55.7%) (both p = 0.001). The high-P group had higher peak progesterone levels (2.1 ± 0.5 ng/ml, p = 0.001), number of oocytes (14.0 ± 5.2) and frozen embryos (4.1 ± 3.5) compared to elective and TEP groups (both p = 0.04). Blastocyst utilization rate was lower (45.7%) than elective freezing and TEP groups but the difference lacked statistical significance (p = 0.33 and p = 0.21, respectively). Cumulative live birth rates were 42.6% in high-P, 59.8% in high-E, 44.7% in elective freezing and 46.7% in TEP groups. Significant predictors of cumulative live birth were female age (aHR: 0.97, 95%CI:0.95–0.99, p = 0.02) and number of frozen blastocysts (aHR:1.05, 95%CI:1.01–1.10), p = 0.02). When adjusted for these confounders, the cumulative live birth rate was not associated with high-E (aHR: 0.86, 95%CI:0.56–1.31) or high-P (aHR: 0.76,95%CI:0.44–1.32). Limitations, reasons for caution This was a retrospective study with small sample size performed at a single fertility center, which may limit the generalizability of our findings. Wider implications of the findings: While lower blastocyst utilization rates are observed in women high late-follicular estradiol or progesterone levels, cumulative live birth rates in subsequent thaw-transfer cycles were not impaired. However, unfavorable outcome parameters observed in women with elevated progesterone deserve further research. Trial registration number Not applicable

The pathology underlying recurrent implantation failures (RIF) is not clear and treatment options proposed are generally not evidence based. Although the effect of heparin on trophoblast biology has not been studied extensively, given the available data suggesting a possible beneficial effect of heparin on embryo implantation, we decided to undertake this pilot study.One hundred and fifty women withor =2 failed assisted reproduction treatment cycles were included in this randomized open-label pilot trial. Participants underwent controlled ovarian stimulation with the long protocol and were randomly allocated to receive 1 mg/kg/day low molecular weight heparin (LMWH) or no treatment in addition to routine luteal phase support (LPS) on the day after oocyte retrieval. LPS and LMWH was continued up to the 12th gestational week in pregnant participants.There were 26 (34.7%) live births in the LMWH group, and 20 (26.7%) in the control group (absolute difference 8.0%, 95% CI -4.2 to 24.9%, P = 0.29). There were 34 (45.3%) and 29 (38.7%) clinical pregnancies in the LMWH and control groups, respectively (absolute difference 6.6%, 95% CI -9.0 to 21.8%, P = 0.41). Implantation rates were 24.5 and 19.8% in the LMWH and control groups, respectively (absolute difference 4.7%, 95% CI -4.7 to 14.1%, P = 0.33).Despite lack of statistical significance, observed relative increase by 30% in live birth rates with LMWH may be regarded as a clinically significant trend necessitating further research on the use of empirical LMWH in women with RIF and possibly in all women undergoing assisted reproduction treatment. Failure to demonstrate statistical significance of the observed treatment difference may be due to limited sample size of this pilot study.

Recent studies indicate a strong paternal influence on embryo development and progression of the embryo to the blastocyst stage. The aim of this study was to compare, during extended culture, the in-vitro development of embryos resulting from intracytoplasmic sperm injection (ICSI) of ejaculated spermatozoa (group 1, n = 347), epididymal (group 2, n = 22) or testicular (group 3, n = 18) spermatozoa from obstructive azoospermic and testicular spermatozoa from non-obstructive azoospermic (group 4, n = 31) subjects. Fertilization and blastocyst formation rates were significantly lower in group 4 (P < 0.05). The incidence of expanded and hatching blastocysts was significantly lower in group 4 (P < 0.05). Overall in 93.2% ejaculate ICSI cycles, blastocysts were transferred on day 5. This was significantly higher than the 62% day 5 transfers in the non-obstructive azoospermic group (P < 0.05). Implantation rate per embryo was significantly higher in the ejaculate ICSI group compared with the other groups (P < 0.05). Clinical pregnancy per transfer was similar between groups; however, significantly fewer multiple pregnancies were encountered in the non-obstructive azoospermic group (P < 0.01). In conclusion, the source of the spermatozoa, most likely to be indicative of the severity of spermatogenic disorder, affects the rate of blastocyst formation and blastocyst implantation. Spermatozoa from non-obstructive azoospermic subjects, when utilized for ICSI, result in embryos that progress to the blastocyst stage at a lower and slower rate and implant less efficiently.

We have shown previously that germ cells recovered from some men with maturation arrest can resume spermatogenesis in vitro and give rise to late elongated spermatids. This study relates the ability of germ cells to differentiate in vitro to the stage at which spermatogenesis is blocked in vivo and to the patient's serum FSH concentration. The presence of germ cells at different stages of spermatogenesis was assessed, before and after culture, by classical cytology, by fluorescence in-situ hybridization and by immunocytochemistry with a germline-specific marker. The proportion of cases of maturation arrest at the primary spermatocyte, secondary spermatocyte and spermatid stage in which in-vitro resumption of meiosis was achieved was 24.3% (9/37), 100% (3/3) and 51.1% (23/45) respectively. Serum FSH concentrations were higher than normal in most cases. However, lower values were measured in patients in whom in-vitro spermatogenesis was achieved compared with those in whom no progression was detected. These data show that, under the conditions of this study, germ cells from men with very high serum FSH concentrations (>20 IU/l) are less likely to resume spermatogenesis in vitro than those coming from men with only moderate increase (10-20 IU/l).

The aim of this study was to determine the effect of 24-h in-vitro culture of testicular spermatozoa in recombinant follicle stimulating hormone (recFSH) supplemented medium versus simple medium on sperm motility, and to analyse the outcome of intracytoplasmic sperm injection (ICSI) of such spermatozoa. A total of 143 positive testicular sperm extraction procedures in men with non-obstructive azoospermia was evaluated prospectively. Extracted testicular tissue samples were randomized to be cultured in vitro for 24 h in simple medium or recFSH supplemented media. ICSI was performed with spermatozoa cultured in recFSH (n = 73) or in simple medium (n = 70). Sperm motility following in-vitro culture, embryo quality after ICSI, and implantation and pregnancy rates were assessed. Of the 898 MII oocytes available in the recFSH group, 646 (71.9%) were injected with spermatozoa showing either twitching or progressive motility. However, only 29.1% of the oocytes in the simple medium group (245/841) were injected with motile spermatozoa (P < 0.05). Fertilization rate (68.8 versus 42.1%), implantation rate per embryo (20.1 versus 13.2%), and clinical pregnancy rate (47. 9 versus 30%) were significantly increased in the recFSH group compared with the simple medium group respectively (P < 0.05). In conclusion, in-vitro culture with recFSH appears to increase the motility of testicular spermatozoa, thus increasing the success of ICSI.

The purpose of this study was to assess the usefulness of sonohysterography in the detection of abnormalities of the uterine cavity in infertile patients, compared with other diagnostic methods. Transvaginal ultrasonography, sonohysterography, hysterosalpingography and finally hysteroscopy were performed in 37 patients with primary and 25 patients with secondary infertility. Suspected uterine anomalies were also confirmed by laparoscopy. Transvaginal ultrasonography and hysterosalpingography were able to detect 36.3 and 72.7% of uterine pathologies respectively. Sonohysterography was able to detect all the anomalies except for a single endometrial polyp (90.3%). However, there was no significant difference between the diagnostic capabilities of these methods. We recommend the use of sonohysterography as an easy, cheap and noninvasive method for the diagnosis of intrauterine pathologies in infertile patients.

A prospective study was performed to determine the feasibility of evaluating the uterine cavity by sonohysterography (SHG) in women who were scheduled for intracytoplasmic sperm injection (ICSI) due to severe male factor infertility and who had not had a previous hysterosalpingography (HSG). Sonohysterography was performed in 80 women scheduled for ICSI. A subsequent hysteroscopy was undertaken in patients with intracavitary lesions. The outcome of ICSI for the women undergoing SHG was compared with that of 240 cycles performed (during the same time period) in patients who had a normal HSG before admission to the clinic. There were no complications attributable to the SHG procedure. Hysteroscopy correctly identified all lesions depicted by SHG. SHG and HSG groups were comparable with regard to female age and duration of infertility. Clinical pregnancy rates per transfer were 40.2% and 42.5% in the SHG and HSG groups, respectively. Abortion rates in the two groups were also similar (14.8 and 11.0%, respectively). In conclusion, sonohysterography appears to be a simple, inexpensive, and safe alternative to HSG for evaluation of the uterine cavity in women scheduled for ICSI.

Since the advent of assisted reproductive technology, the concern about ectopic implantation of embryos has increased dramatically. Simultaneous bilateral tubal pregnancy is the least common type of ectopic implantation of two embryos. In this report we present the first case of simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection (ICSI) and embryo transfer treatment. The present case had no risk factor for ectopic pregnancy. Therefore, for early diagnosis and management of such cases, close clinical follow-up and routine ultrasonography following ICSI are necessary.