BACKGROUND 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. METHODS One hundred and fifty women with ≥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. RESULTS 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). CONCLUSION 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. Clinicaltrials.gov registration number: nCT00750451.
Abstract
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 <4 oocytes or preimplantation genetic test, the study group comprised 459 women who had 699 frozen-thawed embryo transfer cycles.
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
Abstract Study question Do cumulative live birth rates in freeze-all cycles differ between gonadotropin-releasing hormone (GnRH) antagonist protocol and progesterone-primed ovarian stimulation ...(PPOS)? Summary answer GnRH antagonist and PPOS protocols have similar cumulative live birth rates in freeze-all cycles. What is known already GnRH antagonists and progesterone have been used for pituitary suppression in ovarian stimulation cycles. While PPOS protocol has the advantage of oral usage and lower cost, data regarding the laboratory and clinical outcome is limited and confounding. Freeze-all cycles might provide a better model to assess the impact of PPOS protocol and GnRH antagonist protocol on laboratory, clinical outcomes and cumulative live birth rates. Study design, size, duration A retrospective cohort study on IVF cycles performed (n = 568) between January 2020 and May 2022.The entire cohort of embryos were cryopreserved at the blastocyst stage.Inclusion criteria were 18-42 years of age,ICSI for severe male factor infertility.Exclusion criteria were PGD and severe endometriosis.Indications for cryopreservation in the antagonist group were high ovarian response (n:102),endometrial polyps (n:34),high follicular phase P4(n:48) and elective purposes(n:260).PPOS was used due to a transient shortage of GnRH antagonist in the market (n:124). Participants/materials, setting, methods 568 women (GnRH antagonist:444; PPOS:124) were included in the analysis.The primary outcome was the cumulative live birth rate (CLBR) after 3 consecutive embryo transfer cycle, and the secondary outcome parameters were the number of M-II oocytes, fertilization rate and blastocyst utilization rate. Student’s t-test was used for normally distributed continuous data and Fisher’s exact tests for categorical data were used. A generalized estimating equation model and logistic regression analysis were performed to adjust for confounding factors. Main results and the role of chance The mean age of the GnRH antagonist group was 34.1 ± 5.3 and 34.5 ± 5.7 years in PPOS group (p = 0.38). The baseline characteristics including BMI, serum AMH levels, duration of infertility, duration of stimulation and gonadotropin ampules used were similar in both groups. Estradiol and progesterone levels at the time of ovulation trigger were higher in GnRH antagonist cycles (2383.5 ± 1375.4 vs 2034.5 ± 1218.3, p = 0.02 and 0.7 ± 0.6 vs 0.5 ± 0.4, p = 0.01, respectively) The mean number of cumulus-oophorus complexes (12.9 ± 7.4 vs 11.5± 10.0, p = 0.61), M-II oocytes (10.0± 6.1 vs 9.1± 6.1, p = 0.14), frozen blastocysts (4.8± 3.5 vs 4.7± 3.6, p = 0.71) were similar between GnRH antagonist and PPOS groups, respectively. Fertilization rates (84.4% vs 87.2%, p = 0.12) and blastocyst utilization rates (63.4% vs 65.9%, p = 0.34) were also similar between GnRH antagonist and PPOS groups, respectively. The number of transferred embryos and the number of unused blastocysts were similar between groups. The CLBRs after one IVF cycle and 3 consecutive frozen-thawed blastocyst transfers were comparable in GnRH antagonist and PPOS cycles (56.8% and 53.2%, p = 0.37, respectively). Limitations, reasons for caution This was a retrospective study with relatively small sample size performed at a single fertility center, which may limit the generalizability of our findings. Wider implications of the findings If the fresh embryo transfer is not intended, PPOS protocol can be used in all patient types with cost-effective and patient-friendly manner. Trial registration number 2024.013.IRB2.012
In this study, we compared the fertilization rate and embryo quality after intracytoplasmic sperm injection (ICSI) as they relate to oocyte morphology. A total of 654 ICSI cycles yielding 5903 ...metaphase II oocytes were observed. The oocytes retrieved in these cycles were divided into (i) normal oocytes, (ii) oocytes with extracytoplasmic abnormalities (dark zona pellucida and large perivitelline space), (iii) oocytes with cytoplasmic abnormalities (dark cytoplasm, granular cytoplasm, and refractile body), (iv) oocytes with shape abnormalities, and (v) oocytes with more than one abnormality (double and triple abnormalities). Intracytoplasmic vacuoles and aggregates of smooth endoplasmic reticulum were not recorded separately. The fertilization rate and quality of morphologically graded embryos did not differ between the groups. There were 77 cycles where all transferred embryos were derived from abnormal oocytes, and 164 cycles where all embryos were derived from normal oocytes. These cycles were studied further. The two groups were comparable regarding mean female age, duration of infertility, duration of ovarian stimulation, number of ampoules of gonadotrophin injected, and number of oocytes retrieved. Two clinical pregnancy rates (44.4 versus 42.1%) and implantation rates per embryo (10.3 versus 13.2%) were similar. In conclusion, in couples undergoing ICSI, abnormal oocyte morphology is not associated with a decreased fertilization rate or unfavourable embryo quality. Furthermore, embryos derived from abnormal oocytes yield similar clinical pregnancy and implantation rates when transferred compared with embryos derived from normal oocytes.
BACKGROUND: Intracytoplasmic injection of testicular round spermatids has been suggested as a salvage treatment in couples when testicular sperm extraction does not yield any mature sperm. However, ...the success of the procedure is debatable, and controversy surrounds issues such as the presence and (if present) identification of spermatids in testicular tissue. Progression rate to the blastocyst stage of spermatid-derived embryos appears to be low. METHODS: In this study, we investigated the feasibility and outcome of blastocyst stage embryo transfer after round spermatid injection (ROSI). ROSI was undertaken in 58 couples who did not yield mature or elongated sperm to testicular sperm extraction. RESULTS: The incidence of blastocyst formation from two pronuclear oocytes was 7.6%. A total of 16 blastocysts were transferred in 12 patients (20.7%). None of the patients conceived. CONCLUSIONS: The results of this study indicate that the blastocyst stage is reached by only very few ROSI-derived embryos and these embryos do not implant.
Thirty-two infertile couples with obstructive and non-obstructive azoospermia were included in this study. Testicular sperm extraction (TESE) was performed in 16 obstructive azoospermic cases where ...microsurgical sperm aspiration (MESA) or percutaneous sperm aspiration (PESA) were impossible because of totally destroyed epididymis and 16 non-obstructive azoospermia cases with severe spermatogenetic defect where the testicles were the only source of sperm cells. A total of 288 oocytes was obtained from 32 females and 84% were injected. The fertilization rates (FR) with 2 pronuclei (PN) and cleavage rate were 50.8 and 68.2% respectively. A total of 15 pregnancies was achieved (53% per embryo transfer), nine from the obstructive and six from the non-obstructive group. Four pregnancies resulted in clinical abortion (26.6%). The ongoing pregnancy rate was 39.2% per embryo transfer (ET) and 343% per started cycle. A high implantation rate was also achieved (26.6% in non-obstructive and 30% in obstructive azoospermia group). Using testicular spermatozoa in combination with ICSI in both obstructive and non-obstructive azoospermic groups, high implantation and pregnancy rates can be achieved.
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.
In non-obstructive azoospermia spermatozoa can usually only be isolated from the testicles, and thus the most promising treatment model is testicular sperm extraction (TESE). Hormone concentrations, ...testicular volume determinations and testicular biopsy results are not uniform enough to select potential candidates for successful TESE and intracytoplasmic sperm injection (ICSI) approaches in advance. The aim of this study was to assess the efficacy of using ICSI with testicular spermatozoa in cases of non-obstructive azoospermia and to compare the inclusion criteria and sperm existence in the testicles in sperm obtainable and non-obtainable groups. All men showed either complete or incomplete (n = 14) maturation arrest in spermatogenesis, severe hypospermatogenesis (n = 10) or Sertoli cell-only syndrome (n = 5) in their testicular biopsies. Only 14 out of a total of 29 men provided enough spermatozoa for the ICSI procedure, while no spermatozoa were found in the testicular samples of the remaining 15 men. Out of 123 oocytes obtained from 14 females, 101 were injected with the husbands' testicular sperm cells. Total fertilization failure was observed in three cases. Of 39 oocytes fertilized, 38 cleaved. The fertilization and cleavage rates were 38.6 and 97.4% respectively. The pregnancy rate was 20.7% per initiated cycle. In the group from whom spermatozoa were obtainable, the pregnancy rate was 42.9% per initiated cycle and 54.5% per embryo transfer. A total of six pregnancies were achieved, of which two Were twins and four were singletons. One singleton pregnancy resulted in abortion in the first trimester. There was no statistical difference concerning the serum follicle stimulating hormone concentration, testicular volume and biopsy results in groups in which spermatozoa were obtainable or not. In conclusion, although the association of TESE with ICSI obtained pregnancies for some patients with non-obstructive azoospermia, further studies are needed to determine the inclusion criteria for successful TESE.
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