Subcutaneous progesterone administration provides a similar ongoing pregnancy rate compared with intramuscular progesterone administration in hormone replacement therapy frozen embryo transfer cycles.

Objective: To compare the ongoing pregnancy rates (OPRs) for subcutaneous progesterone (SC-P) to intramuscular progesterone (IM-P) in hormone replacement therapy used in frozen embryo transfer (FET) cycles. Design: Prospective nonrandomized cohort study. Setting: Private fertility clinic. Patients: The study enrolled 224 patients scheduled for hormone replacement therapy (HRT)-FET cycles with SC-P (n = 133) or IM-P (n = 91). The route of P administration was decided according to the patient's preference and accessibility to the hospital. In the first FET cycle of a freeze-all cycle using single blastocyst transfers, a woman aged ≤35 was included. Main Outcomes: Ongoing pregnancy (OP). Results: The demographic, cycle, and embryologic characteristics were similar between groups. The clinical pregnancy rates (86/133[64.7%] vs. 57/91[62.6%]); miscarriage rates (21/86 [24.4%] vs. 10/57 [17.5%]), and OPR (65/133 [48.9%] vs. 47/91 [51.6%]) were comparable between the SC-P and IM-P groups. Binary logistic regression for OP as the dependent factor revealed that blastocyst morphology was found to be a significant independent prognosticator (for poor quality embryos adjusted odds ratio, 0.11; 95% confidence interval, 0.029-0.427) and progesterone route (SC-P vs. IM-P) was an insignificant prognosticator (adjusted odds ratio, 0.694; 95% confidence interval, 0.354-1.358). Conclusions: The OPR for SC-P administration was similar to that for IM-P in HRT-FET cycles. The effect of ET-day P levels may vary regarding the administration route. Randomized controlled trials comparing different P administration routes are needed, and large-scale prospective trials are warranted to evaluate the ET-day P levels on pregnancy outcome.

The number of prior pregnancy losses does not impact euploidy rates in young patients with idiopathic recurrent pregnancy loss.

PURPOSE: Our study aimed to determine the possible factors that might impact the probability of obtaining a euploid blastocyst following intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A) procedures in idiopathic recurrent pregnancy loss (RPL) patients. METHODS: This single-center retrospective cohort analysis included 180 oocyte retrieval cycles of 166 women under 35 years old and those diagnosed with idiopathic RPL according to American Society of Reproductive Medicine (ASRM) guidelines. Trophectoderm biopsy and next-generation sequencing (NGS) were the techniques used. Patients were stratified by the number of previous losses (Group A: 2, Group B: 3, and Group C: > 3). RESULTS: Baseline and embryological characteristics showed no statistically significant differences. The euploidy rate per analyzed blastocyst was comparable within the groups (63.3%, 58.2%, and 58.5%; p = 0.477). Logistic regression analyses confirmed that only the trophectoderm scores of A and B increased the probability of obtaining a euploid embryo [OR: 1.82, 95% CI (1.120-2.956), p: 0.016]. CONCLUSION: It is concluded that there was no correlation between the number of previous losses and the chance of finding at least one euploid embryo in ICSI cycles of women younger than 35 years.

Impact of trophoectoderm biopsy for preimplantation genetic testing on serum ß-hCG levels, time of delivery and birthweight following frozen embryo transfer cycles.

Aim: This study investigated whether trophoectoderm (TE) biopsy adversely impacts serum ß-human chorionic gonadotropin (hCG) level on the 15th day of embryo transfer (ET), delivery week and birthweight, between biopsied and unbiopsied embryo groups, in a cohort of women who delivered a singleton baby, following frozen-thawed ET.Methods: All women having had a live birth after blastocyst ETs following frozen ET cycles with preimplantation genetic testing (PGT) were included. A control group was selected among women who had a live birth following single frozen blastocyst transfer without PGT-A at the same period in our clinicResults: One hundred fifteen and 173 cycles with- and without-PGT, respectively, were included. Serum ß-hCG level on the 15th day after ET was comparable between the groups (p = .336). Average birthweight of the babies born following biopsied embryos were significantly lower (3200 vs. 3380; p = .027). Women who received trophectoderm biopsied embryos had a significantly higher probability of having a baby weighing ≤1500 g and 1500-2500 g (p = .022) or ≤2500 g (p = .008). Proportion of preterm delivery was significantly higher in the biopsy group (p = .023). However, after adjusting for potential covariates, trophectoderm biopsy did not seem to increase the risk of preterm birth (OR 1.525; 95% CI, 0,644-3.611; p = .338)Conclusions: TE biopsy does not seem to impact serum ß-hCG level on the 15th day after ET. Average birthweight is lower when a biopsied embryo was transferred. After adjusting for potential covariates, trophectoderm biopsy does not seem to increase the risk of preterm birth.

Which factors affect the likelihood of miscarriage after single euploid blastocyst transfer?

RESEARCH QUESTION: Which parameters affect the likelihood of miscarriage after single euploid frozen-thawed blastocyst transfer (FBT)? DESIGN: In this retrospective study, clinical and laboratory data from 1051 single euploid FBTs were evaluated. Exclusion criteria were endocrine or systemic pathologies, uterine anomalies or pathologies, unilateral or bilateral hydrosalpinx, karyotypic abnormalities (either maternal or paternal) or thrombophilia. Patients were divided into two groups according to pregnancy outcome: live birth and miscarriage. RESULTS: Body mass index (BMI) (25.98 ± 0.5 versus 24.36 ± 0.21, P = 0.019), duration of infertility (6.62 ± 0.54 versus 4.92 ± 0.18, P = 0.006) and number of previous miscarriages (1.36 ± 0.13 versus 0.79 ± 0.05, P < 0.001) were significantly higher in the miscarriage group (n = 100) than in the live birth group (n = 589). Although the trophectoderm and inner cell mass (ICM) percentage scores were not statistically different among the miscarriage and live birth groups, the percentage of day-6 biopsied embryos was significantly higher in the miscarriage group. Binary logistic regression analysis revealed that BMI (OR 1.083, 95% CI 1.013 to 1.158, P = 0.02) and number of previous miscarriages (OR 1.279, 95% CI 1.013 to 1.158, P = 0.038) were independent factors for miscarriage. Patients with elevated BMI and a higher number of miscarriages were at increased risk of miscarriage. CONCLUSION: After a single euploid FBT, BMI and number of previous miscarriages are predictors of miscarriage. Lifestyle interventions before FBT may decrease miscarriage rates.

Euploidy rates of embryos in young patients with good and low prognosis according to the POSEIDON criteria.

RESEARCH QUESTION: Does an association exist between ovarian reserve, ovarian response and embryonic euploidy in female patients under age 35 years? DESIGN: This was a retrospective analysis of intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidies cycles among patients enrolled at Bahceci Fulya IVF Center between January 2016 and August 2019. A total of 133 patients in POSEIDON group 1 (suboptimal responder; female age <35 years, antral follicle count [AFC] ≥5, number of oocytes retrieved <10) (group A), 133 patients in POSEIDON group 3 (expected low responder; female age <35 years, AFC <5) (group B) and 323 in the non-low-prognosis group (female age <35 years, AFC ≥5 and number of oocytes retrieved >9) (group C) were included. RESULTS: There was no significant difference in euploidy rate per embryo among the three groups (61.7% [145/235] for group A versus 53.5% [68/127] for group B versus 62% [625/1008] for group C; P = 0.13). The cancellation rate in cycles without a euploid blastocyst was significantly lower in group C than groups A and B (8.4% versus 12.8% and 16.5%; P = 0.034). Multivariate regression analysis indicated that the ovarian response group did not significantly affect the probability of obtaining a euploid embryo. Trophectoderm score 'C' (odds ratio 0.520, P = 0.007) and inner cell mass score 'C' (odds ratio 0.480, P < 0.001) were associated with a decreased probability of obtaining a euploid embryo. CONCLUSIONS: These results confirm that POSEIDON group 1 and group 3 and non-low-prognosis patients have different probabilities of euploid embryos being obtained per cycle. However, euploidy rates per embryo are not affected by the patient's ovarian reserve and response.

The impact of patient, embryo, and translocation characteristics on the ploidy status of young couples undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) by next generation sequencing (NGS).

PURPOSE: To evaluate the factors that affect the incidence of euploid balanced embryos and interchromosomal effect (ICE) in carriers of different structural rearrangements. METHODS: This retrospective study includes 95 couples with reciprocal translocations (RecT) and 36 couples with Robertsonian translocations (RobT) undergoing Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) between March 2016 and July 2019. Next-generation sequencing (NGS) was the technique used coupled with trophectoderm (TE) biopsy. Only cases with females under 38 years were included. A total of 532 blastocysts were evaluated. RESULTS: The euploidy rate was similar in RobT when compared with RecT carriers [57/156 (36.5%) vs. 112/376 (29.8%), p = 0.127]. The pure ICE rate was significantly higher in RobT carriers [48/156 (30.8%) vs. 53/376 (14.1%), p < 0.001] than it was in RecT carriers. Female age was the independent factor for the probability of obtaining a euploid embryo in RecT and RobT carriers, and increasing female age decreases the probability of obtaining a euploid embryo. In RecT carriers, no significant differences were observed in euploidy rates, pure ICE, or combined ICE according to the length of the translocated fragment and the chromosome group. However, total ICE was significantly lower when there was a breakpoint in the short chromosome arm together with a breakpoint in the long arm [(44/158 (27.8%) for pq or qp, 51/155 (32.9%) for pp and 30/63 (47.6%) for qq; p = 0.02]. CONCLUSION: The incidence of euploid/balanced blastocysts was similar in both types of translocations. However, there was a significant increase in pure ICE in RobT compared to RecT carriers. In RecT carriers, the presence of the breakpoints in the long arm of the chromosomes involved in the rearrangement resulted in a higher total ICE.

Elevation of progesterone on the trigger day exerts no carryover effect on live birth in freeze-all cycles.

AIM: To evaluate the effect of trigger day progesterone (P) levels on live birth in freeze-all cycles. MATERIAL AND METHODS: Retrospective analysis of 1034 freeze-all female patients aged <38 years with single blastocyst transfers. Patients with (n = 268) or without (n = 766) preimplantation genetic test for aneuploidy (PGT-A) arm were further categorized into three subgroups based on trigger day P levels; low (<0.80 ng/ml), medium (0.8-1.49 ng/ml), and high (≥1.50 ng/ml). RESULTS: Estradiol (E2) levels on trigger day, the number of oocytes retrieved and the number of mature oocytes increased significantly with increasing serum p values in cycles without and with PGT-A arms. Significant correlation was found between E2 levels on trigger day and serum P levels and between the number of total oocytes retrieved and serum P levels Live birth rates were similar in the three subgroups in without PGT-A arm (51%, 52.6%, and 51.5%, respectively; p = .922) and with PGT-A arm (55.1%, 55.1%, and 62.5%, respectively; p = .730). Multivariate regression analysis revealed that trigger day P levels were not significant for live birth. CONCLUSION: The proposal that trigger day progesterone elevation (PE) exerts a detrimental effect on oocyte and embryo competence has no clinical validity.

Being on the side of old findings: progesterone elevation on the day of oocyte maturation induction does not affect embryological parameters throughout the blastocyst culture period.

PURPOSE: To investigate whether there is any detrimental effect of progesterone elevation (PE) on the day of oocyte maturation induction on embryological development potentials. METHODS: This retrospective single-center cohort study included a total of 1485 individual intracytoplasmic sperm injection (ICSI) cycles between January 2014 and December 2018. Serum progesterone (P) levels were measured on the day of oocyte maturation induction following the GnRH antagonist suppression protocol. Embryological parameters such as maturation, fertilization rate (FR), top-quality embryo (TQE) formation rate per 2PN on day 3, and excellent-quality blastocyst (EQB) formation rate per 2PN on day 5/6 were recorded. The inclusion criteria for women were an age ≤ 37 years, a BMI ≤ 30 kg/m2, and access to a total sperm concentration ≥ 2 million. Groups were stratified according to the serum P levels using the cut-off levels of < 0.8 ng/ml; 0.8-1.49 ng/ml; and ≥ 1.5 ng/ml. RESULTS: Peak E2 level and total number of oocytes retrieved were significantly related to PE (p < 0.001). FR did not display a significance difference between groups (p = 0.108). The TQE and the blastulation rates were not affected by PE (p = 0.82 and p = 0.68, respectively). Chi square analysis revealed a significant relationship between PE and the EQB formation rate (p = 0.01). GEE analysis failed to present any statistical significance regarding the effect of PE on neither the TQE nor the EQB formation rates per 2PN [OR 1.07; 95% (0.98-1.16) p = 0.113 and OR 0.93; 95% (0.80-1.07) p = 0.32, respectively]. CONCLUSIONS: In accordance with previously published papers, our study could not find any detrimental effect of PE on embryological outcomes throughout the blastocyst culture period.

Comparison of intramuscular versus subcutaneous aqueous progesterone for luteal phase support in artificially prepared frozen embryo transfer cycles.

OBJECTIVE: Cryopreservation of embryos for future transfer attempts has noticeably increased in the last decade, especially due to the technological developments in in vitro fertlization (IVF) laboratories. In parallel, different progesterone (P) replacement regimens preceding artificially prepared frozen embryo transfer (AC-FET) attempts, especially with respect to the route of application and dosing scheme, have been widely argued so far. We aimed to provide more information about the efficacy profile of novel subcutaneous aqueous progesterone (SP) in AC-FET cycles. MATERIALS AND METHODS: This retrospective, single-centre cohort study included a total of 507 AC-FET cycles performed between June 2018 and April 2020. Three hundred forty-nine (68.8%) patients received 50 mg of intramuscular progesterone as once daily, 158 (31.2%) patients received 25 mg of SP as twice daily. Only, the first and single blastocyst transfers from the same cohort were accepted. The inclusion criteria were as follows: females aged <37 years, body mass index ≥18 kg/m2 and ≤35 kg/m2, sperm concentration ≥5x106/mL. Pre-implantation genetic testing cycles were not included. The primary outcome was the live birth rate (LBR). RESULTS: The number of previous IVF attempts, type of infertility, peak estradiol (E2) levels, the total number of retrieved oocytes, mature oocytes, and the number of 2PN was significantly different between the groups. Positive pregnancy (p=0.474) and clinical pregnancy rates (p=0.979), LBR (p=0.404), and missed abortion rates (p=0.144) were comparable between the groups. The total number of oocytes [adjusted odds ratios (AOR)=1.024, 95% confidence interval (CI): 1.002-1.047; p=0.03)], endometrial thickness (AOR=1.121, 95% CI: 1.003-1.253; p=0.044), and cryopreservation day 5/6 (AOR=0.421, 95% CI: 0.226-0.788; p=0.007) achieved statistical significance following binary logistic regression analysis. However, P administration type did not achieve statistical significance (p=0.731). CONCLUSION: As a novel option, SP has comparable efficacy in pregnancy outcomes and may be accepted as an alternative for luteal phase support in AC-FET cycles.

Impact of elective frozen vs. fresh embryo transfer strategies on cumulative live birth: Do deleterious effects still exist in normal & hyper responders?

BACKGROUND: Is freeze-all strategy effective in terms of cumulative live birth rates (CLBRs) in all patients? METHODS: This retrospective single-center study analyzed the CLBRs of 2523 patients undergoing fresh or electively frozen blastocyst transfer cycles. In 1047, cycles, the fresh embryo transfer (ET) strategy was applied for the 1st ET, whereas electively frozen ET (e-FET) was performed in 1476 cycles. Female age ≤ 37 and blastocysts frozen via vitrification were included. The patients in each arm were further stratified into four subgroups according to the number of oocytes retrieved as follows: Group A: 1-5, group B: 6-10, group C: 11-15 and group D: 16-25 oocytes retrieved. The primary endpoint was the CLBR. The secondary endpoints were the ovarian hyperstimulation syndrome (OHSS) rate and the live birth rates (LBRs) following fresh ETs and e-FETs for the first transfers. RESULT(S): The CLBR was similar between the fresh ET and e-FET arms in group A (35/76 (46.1%) vs 29/67 (43.3%), p = 0.74) and group B (165/275 (60%) vs 216/324 (66.7%), p = 0.091), whereas significantly higher rates were detected in favor of the e-FET arm within group C (328/460 (71.3%) vs 201/348 (57.8%), p<0.001) and group D (227/348 (65.2%), vs 446/625 (71.5%), p<0.001). The OHSS rate was also found to be higher in the fresh ET arm among group C (12/348 (3.4%) vs 0/460 (0%), p<0.001) and group D (38/348 (10.9%) vs 3/625 (0.5%), p<0.001) patients than e-FET arm. Perinatal and obstetrical outcomes were nonsignificantly different between fresh and e-FET arms. However, the birth weights were significantly lower for fresh ET, 3064 versus 3201 g for singletons (p<0.001). CONCLUSION: Compared with a fresh-transfer strategy, the e-FET strategy resulted in a higher CLBR among patients with >10 oocytes retrieved during stimulated cycles.

Parameters impacting the live birth rate per transfer after frozen single euploid blastocyst transfer.

BACKGROUND: To assess the predictive value of patient characteristics, controlled ovarian stimulation and embryological parameters on the live birth outcome of single euploid frozen-warmed blastocyst transfer (FBT). METHODS: This was a retrospective cohort study including 707 single FBTs after preimplantation genetic testing for aneuploidy (PGT-A) that were performed from October 1, 2015, to January 1, 2018. The effects of patient-, cycle- and embryology-related parameters on the live birth outcome after FBT were assessed. RESULTS: In the subgroup analysis based on live birth, patients who achieved a live birth had a significantly lower body mass index (BMI) than patients who did not achieve a live birth (22.7 (21.5-24.6) kg/m2 vs 27 (24-29.2) kg/m2, p<0.001). The percentage of blastocysts with inner cell mass (ICM) A or B was significantly higher among patients achieving a live birth, at 91.6% vs. 82.6% (p<0.001). Day-5 biopsies were also more prevalent among patients achieving a live birth, at 82.9% vs 68.1% (p<0.001). On the other hand, the mitochondrial DNA (mtDNA) levels were significantly lower among cases with a successful live birth, at 18.7 (15.45-23.68) vs 20.55 (16.43-25.22) (p = 0.001). The logistic regression analysis showed that BMI (p<0.001, OR: 0.789, 95% CI [0.734-0.848]), day of trophectoderm (TE) biopsy (p<0.001, OR: 0.336, 95% CI [0.189-0.598]) and number of previous miscarriages (p = 0.004, OR: 0.733, 95% CI [0.594-0.906]) were significantly correlated with live birth. Patients with elevated BMIs, cycles in which embryos were biopsied on day-6 and a higher number of miscarriages were at increased risks of reduced live birth rates. CONCLUSION: A high BMI, an embryo biopsy on day-6 and a high number of miscarriages negatively affect the live birth rate after single euploid FBT.

Measuring the serum progesterone level on the day of transfer can be an additional tool to maximize ongoing pregnancies in single euploid frozen blastocyst transfers.

BACKGROUND: Endometrial preparation with hormone replacement therapy (HRT) is the preferred regimen for clinicians due to the opportunity to schedule the day of embryo transfer and for patients due to the requirement of fewer visits for frozen-warmed embryo transfers (FET). The increasing number of FETs raises the question of the serum P levels required to optimize the pregnancy outcome on the embryo transfer day. METHODS: This prospective cohort study includes patients who underwent single euploid FET. All patients received HRT with oestradiol valerate (EV) and 100 mg of intramuscular (IM) progesterone (P). FET was scheduled 117-120 h after the first IM administration of 100 mg P. The serum P level was analyzed 1 h before the embryo transfer (ET). In all cycles, only embryos that were biopsied on day 5 were utilized for FET. Next generation sequencing (NGS) was used for comprehensive chromosomal analysis. RESULTS: Overall, the ongoing pregnancy rate (OPR) was 58.9% (99/168). Data were then categorized according to the presence (Group I; n = 99) or the absence (Group II; n = 69) of an ongoing pregnancy. No significant differences regarding, female age, body mass index (BMI), number of previous miscarriages, number of previous live birth, sperm concentration, number of oocytes retrieved, number of mature oocytes (MII), rate of fertilized oocytes with two pronuclei (2PN), trophectoderm score, inner cell mass (ICM) score, endometrial thickness (mm), oestrodiol (E2) and P levels prior to IM P administration were found between two groups. The P levels on the day of ET (ng/ml) were significantly higher in Group I (28 (5.6-76.4) vs 16.4 (7.4-60) p = 0.039). The P level on the day of ET was a predictor of a higher OPR (p < 0.001 OR: 1.033 95%CI [1.009-1.056]) after multivariate analysis. The ROC curve showed a significant predictive value of serum P levels on the day of ET for OPR, with an AUC (95%CI) = 0.716 (0.637-0.795). The optimal cut-off value for prediction of the OPR was a P level of 20.6 ng/ml (71.7% sensitivity, 56.5% specificity). CONCLUSIONS: The present study suggests a minimum threshold of the serum P value on the day of ET that needs to be reached in HRT cycles to optimize the clinical outcome. Individualization of the P dosage should be evaluated in further studies.

The impact of serum oestradiol concentration prior to progesterone administration on live birth rate in single vitrified-warmed blastocyst transfer cycles.

RESEARCH QUESTION: Can serum oestradiol concentrations on the day of progesterone initiation predict live birth rates in single, autologous vitrified-warmed blastocyst transfers following artificial endometrial preparation? DESIGN: This retrospective study included the first transfers of 468 patients with unexplained or tubal factor infertility who underwent freeze-all cycles using single, top-quality blastocysts after artificial endometrial preparation from January 2015 to January 2018. Patients were stratified into four groups based on serum oestradiol concentration percentiles on the day of progesterone initiation: Group 1 (<25th percentile), Group 2 (25-50th percentile), Group 3 (51-75th percentile) and Group 4 (>75th percentile). The primary outcome was live birth rate. The secondary outcomes were implantation, clinical pregnancy and multiple pregnancy rates. Receiver operating characteristic (ROC) curves were generated to evaluate serum oestradiol concentrations in predicting implantation, clinical pregnancy and live birth. RESULTS: Similar live birth rates of 51.6%, 55.1%, 54.9% and 56.4% for Groups 1, 2, 3 and 4, respectively, were found. The groups also showed similar implantation and clinical pregnancy rates. ROC analysis revealed that serum oestradiol concentrations on the day of progesterone initiation were not predictive for implantation (area under the curve [AUC] 0.490, 95% CI 0.445-0.554), clinical pregnancy (AUC 0.507, 95% CI 0.453-0.561) or live birth (AUC 0.514, 95% CI 0.461-0.566). CONCLUSIONS: Serum oestradiol concentration monitoring just prior to progesterone administration does not appear to be predictive for live birth rates in good prognosis patients undergoing single, autologous vitrified-warmed blastocyst transfer after artificial endometrial preparation. Therefore, the current practice of monitoring serum oestradiol concentration is not supported by this study.

Comparison of daily vaginal progesterone gel plus weekly intramuscular progesterone with daily intramuscular progesterone for luteal phase support in single, autologous euploid frozen-thawed embryo transfers.

PURPOSE: To compare outcomes between daily intramuscular progesterone (IMP) and daily vaginal progesterone (VP) gel plus weekly intramuscular hydroxyprogesterone caproate (IMHPC) for luteal phase support (LPS) in single, autologous euploid frozen-thawed blastocyst transfers (FBTs) following artificial endometrial preparation (EP). METHODS: The retrospective cohort study included 767 single, autologous FBTs from 731 patients between January 2015 and March 2018. LPS was performed either with IMP (100 mg/day) or with VP gel (90 mg, twice daily) plus IMHPC (250 mg/week). Oral estrogen was prescribed in combination of both regimes. Oral estrogen was discontinued following the visualization of fetal cardiac activity on ultrasound and progesterone at 10 weeks of gestation. The primary outcome was live birth rate. The secondary outcomes included implantation, clinical pregnancy, and multiple pregnancy rates. RESULTS: Patient characteristics did not differ in LPS regimes. Of 767 FBTs, 608 had IMP (100 mg/day) for LPS and 159 had VP gel (90 mg, twice daily) plus IMHPC (250 mg/week) for LPS. The live birth rate was 51.8% and 50.3%, respectively (p = 0.737, OR 0.94, 95%CI 0.66-1.33). The implantation rate was 62.7% and 64.2%, respectively (p = 0.730, OR 1.06, 95%CI 0.74-1.53). The clinical pregnancy rates were also similar in both groups (59.5% vs. 61.6%, respectively, p = 0.631, OR 1.09, 95%CI 0.76-1.56). CONCLUSIONS: We did not observe significant differences in the rates of live birth, implantation, and clinical pregnancy between daily IMP and daily VP gel plus weekly IMHPC for LPS in single, autologous euploid FBTs after artificial EP.

The impact of endometriosis on early embryo morphokinetics: a case-control study.

The aim of this study was to evaluate the possible effects of endometriosis on early embryo development, by comparing the morphokinetic development of embryos obtained from women with clinically confirmed endometriosis with the ones obtained from tubal factor infertility cases. A total of 82 cycles/patients including 53 cycles with endometriosis and 29 cycles with tubal factor infertility were evaluated. A total of 439 embryos were scored for embryo morphokinetics. Age, body mass index, fertilization rates were similar within the groups. However, the number of previous ART trials was found to be higher (p < 0.05) in the study group. Also, the number of retrieved oocytes and M2 oocytes were found to be significantly lower in patients with endometriosis (p < 0.01). The duration of the first cell cycle (ECC1) and S2 (the time between t3 and t4) displayed significant distortions compared with embryos in the control group. All other analyzed early morphokinetic parameters (t2, t3, t4, t5, t6, t7, t8) and duration of events (VP, cc2a, ECC2, ECC3, S3) showed similar values between study and control groups, respectively. In the light of these findings, it is apparent that endometriosis predominantly affects the duration of the early morphokinetic events and cell cycles.

A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family.

PURPOSE: The purpose of this study was to identify mutations that cause non-syndromic male infertility using whole exome sequencing of family cases. METHODS: We recruited a consanguineous Turkish family comprising nine siblings with male triplets; two of the triplets were infertile as well as one younger infertile brother. Whole exome sequencing (WES) performed on two azoospermic brothers identified a mutation in the melanoma antigen family B4 (MAGEB4) gene which was confirmed via Sanger sequencing and then screened for on control groups and unrelated infertile subjects. The effect of the mutation on messenger RNA (mRNA) and protein levels was tested after in vitro cell transfection. Structural features of MAGEB4 were predicted throughout the conserved MAGE domain. RESULTS: The novel single-base substitution (c.1041A>T) in the X-linked MAGEB4 gene was identified as a no-stop mutation. The mutation is predicted to add 24 amino acids to the C-terminus of MAGEB4. Our functional studies were unable to detect any effect either on mRNA stability, intracellular localization of the protein, or the ability to homodimerize/heterodimerize with other MAGE proteins. We thus hypothesize that these additional amino acids may affect the proper protein interactions with MAGEB4 partners. CONCLUSION: The whole exome analysis of a consanguineous Turkish family revealed MAGEB4 as a possible new X-linked cause of inherited male infertility. This study provides the first clue to the physiological function of a MAGE protein.

PGD management scheme for older females with balanced translocations: Do older females have less chance of balanced embryo transfer?

OBJECTIVE: Carriers of reciprocal and Robertsonian translocations have a higher risk of experiencing infertility and repeated miscarriages. It is well established that with advancing maternal age, the risk of aneuploidies in embryos increases. In this study, the chance of developing balanced embryos in translocation carriers with advanced maternal age was analyzed to establish a management scheme for couples seeking fertility treatment and preimplantation genetic diagnosis (PGD). MATERIAL AND METHODS: Biopsy was performed on cleavage-stage embryos. Multicolor fluorescence in situ hybridization was used for PGD. The translocation carriers underwent a total of 55 cycles of PGD. Genetics diagnosis and cycle outcomes of PGD cases were examined. RESULTS: This study showed that the chance of obtaining a balanced embryo from the Robertsonian translocation carriers was significantly less when the maternal age is advanced. Similar rates for balanced embryos were obtained from the reciprocal translocation carriers. CONCLUSION: The results of this study show that maternal age plays an important role and that genetic counselling and planning for a PGD cycle in translocation carriers, particularly for Robertsonian carriers, must be accordingly adapted.

Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family.

Infertility is a global healthcare problem, and despite long years of assisted reproductive activities, a significant number of cases remain idiopathic. Our currently restricted understanding of basic mechanisms driving human gametogenesis severely limits the improvement of clinical care for infertile patients. Using exome sequencing, we identified a nonsense mutation leading to a premature stop in the TEX15 locus (c.2130T>G, p.Y710*) in a consanguineous Turkish family comprising eight siblings in which three brothers were identified as infertile. TEX15 displays testis-specific expression, maps to chromosome 8, contains four exons and encodes a 2789-amino acid protein with uncertain function. The mutation, which should lead to early translational termination at the first exon of TEX15, co-segregated with the infertility phenotype, and our data strongly suggest that it is the cause of spermatogenic defects in the family. All three affected brothers presented a phenotype reminiscent of the one observed in KO mice. Indeed, previously reported results demonstrated that disruption of the orthologous gene in mice caused a drastic reduction in testis size and meiotic arrest in the first wave of spermatogenesis in males while female KO mice were fertile. The data from our study of one Turkish family suggested that the identified mutation correlates with a decrease in sperm count over time. A diagnostic test identifying the mutation in man could provide an indication of spermatogenic failure and prompt patients to undertake sperm cryopreservation at an early age.

Is the interchromosomal effect present in embryos derived from Robertsonian and reciprocal translocation carriers particularly focusing on chromosome 10 rearrangements?

The aim of this study was to analyse the possible occurrence of the interchromosomal effect (ICE) in human preimplantation embryos obtained from Robertsonian and reciprocal translocation carriers focusing on ones with chromosome 10 rearrangements who were undergoing preimplantation genetic diagnosis (PGD) and to investigate whether offering aneuploidy screening would be beneficial to these patients. Cleavage stage embryos from translocation carriers undergoing PGD were biopsied. Multicolour fluorescence in situ hybridisation for the chromosomes involved in the translocation in addition to nine more chromosomes (13, 15, 16, 17, 18, 21, 22, X and Y) was used in the analysis. The control group involved embryos obtained from age-matched patients undergoing preimplantation genetic screening (PGS). Cumulative aneuploidy rate in embryos derived from both Robertsonian and reciprocal translocation carriers was found to be similar with the control group. Therefore no ICE was observed in cleavage stage embryos obtained from these carriers. More than half of the embryos with chromosome 10 rearrangements had aneuploidy for which an increased aneuploidy rate was more apparent in male carriers. Thus, it is possible that there is a risk of ICE in reciprocal carriers with chromosome 10 rearrangements. This study showed that there is no ICE in embryos derived from Robertsonian and reciprocal translocation carriers. However high rates of aneuploidy in structurally normal chromosomes were detected in embryos derived from these carriers and thus aneuploidy screening in addition to PGD may increase the pregnancy rates of these patients.