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Purpose There is no consensus yet in the literature on an optimal luteinizing hormone (LH) level for human chorionic gonadotrophin (hCG) trigger timing in patients undergoing frozen-thawed embryo transfer (FET) with modified natural cycles (mNC). The objective of our study was to compare the clinical results of hCG trigger at different LH levels in mNC-FET cases. Methods This retrospective study was conducted in Istanbul Memorial Hospital ART and Genetics Center. A total of 1076 cases with 1163 mNC-FET cycles were evaluated. LH levels between the start of LH rise (15 IU/L) and LH peak level (> 40 IU/L) were evaluated. Cycles were analyzed in four groups: group A (n = 287) LH level on the day prior to the day of hCG; groups B, C and D, LH levels on the day of hCG: group B (n = 245) LH 15–24.9; group C (n = 253), LH 25–39.9; group D (n = 383) LH ≥ 40. Cycle outcomes in the four groups were compared. Results Subgroup analyses of mNC-FET groups showed that implantation, clinical and ongoing pregnancy rates, and pregnancy losses were not significantly different in patients with different LH levels on the day of hCG trigger. Conclusion Our study suggests that hCG can be administered at any time between the start of LH rise (≥ 15 IU/L) and LH peak level (≥ 40 IU/L) without a detrimental effect on clinical outcome.

PURPOSE: To evaluate embryology and pregnancy outcomes following individual and group embryo culture in the setting of contemporary laboratory practices and freeze-all cycles. METHODS: Patients underwent ovarian stimulation followed by intracytoplasmic sperm injection (ICSI). Embryos proceeded through individual culture and then underwent preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy. In a subsequent cycle, participants underwent single embryo transfer of a vitrified-warmed, euploid embryo. Outcomes were compared to controls undergoing group culture during the same time frame. The Mann-Whitney U test and logistic regression models were utilized. RESULTS: Outcomes were assessed for 144 patients whose embryos underwent individual culture and 449 controls whose embryos underwent group culture. There were no significant differences in fertilization rates between groups (81.7% for individual culture vs. 84.1% for group culture, p = 0.22). However, individual culture was associated with a decreased rate of blastocyst formation compared to group culture (43.5% vs. 48.5%, p < 0.01). Following single, vitrified-warmed euploid blastocyst transfer, there were no significant differences between individual culture and group culture, respectively, in rates of positive βhCG (81.9% vs. 81.5%, p = 0.91), sustained implantation (63.9% vs. 65.0%, p = 0.80), biochemical miscarriage (16.7% vs. 12.3%, p = 0.18), or clinical miscarriage (1.4% vs. 4.2%, p = 0.13). CONCLUSION: While individual culture appears to negatively impact the rate of usable blastocyst formation compared to group culture, there were no significant differences in pregnancy outcomes following transfer of a single, vitrified-warmed euploid blastocyst.

PURPOSE: To establish blastocyst freezing criteria for day 7 blastocyst (day 7 BL) for single vitrified-warmed blastocyst transfer (SVBT) by examining the diameter of blastocysts. METHODS: Patients who underwent day 7 BL transfer cycles (1143 cycles, mean age: 38.5 ± 3.5) and randomly selected patients after 1:1 matching who underwent day 6 BL transfer cycles and day 2-single-embryo transfer (SET) cycles were used for analysis. Comparison of the miscarriage (per clinical pregnancy) and live birth rates were made among day 2-SET, day 7 BL, and day 6 BL. These blastocyst groups were stratified into six groups based on blastocyst diameter, namely, 180 μm, 190 μm, 200 μm, 210 μm, over 220 μm, and hatched, for making the freezing criteria. RESULTS: For each diameter, 180 μm, 190 μm, 200 μm, 210 μm, over 220 μm, and hatched, the live birth rates of day 7 BL after SVBT were 9.0%, 11.9%, 11.5%, 15.6%, 20.0%, and 19.9%, respectively. Compared with the 14.6% live birth rate of the day 2-SET group, the live birth rate of 220 μm day 7 BL was significantly higher (P < 0.05) and was around the same in other diameter groups. CONCLUSION: Our study demonstrates that sufficient live birth rates can be obtained after SVBT even from blastocysts on day 7 when blastocysts were vitrified at expanded blastocyst stage of over 180 μm of diameter or at hatched blastocyst stage and were transferred at the optimal time. This is the first study to establish a day 7 blastocyst freezing criteria using blastocyst diameter, which is an objective assessment way.

PURPOSE: This study evaluated the potential viability of embryos with low mosaicism level (

PURPOSE: The aim of the study was to compare the levels of angiogenic markers and markers of placentation between pregnancies conceived with fresh (ET) and vitrified-warmed blastocyst transfer (FET). METHODS: Women with singleton pregnancies resulting from fresh ET or FET during the period between 2013 and 2017 were included in this prospective observational study. Fresh ET was performed in a stimulated and FET in natural cycle. At 6–7 weeks of gestation, after ultrasound confirmation of a single gestational sac with a viable embryo, serum levels of free β-hCG, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PIGF) and fms-like tyrosine kinase (sFlt-1) were measured. Data on the patients’ characteristics, pregnancy complications and outcomes were collected from a questionnaire and National Perinatal Information System of Slovenia. RESULTS: Among 211 pregnancies, 126 were achieved with fresh ET and 85 with FET. There were no significant differences in perinatal outcome, pregnancy complication and PIGF level between the fresh ET and FET group. Women achieving pregnancy with FET had significant higher levels of free β-hCG (40.20 ± 30.62 IU/L vs. 28.74 ± 23.52, p = 0.002), PAPP-A (0.09 ± 0.06 vs. 0.06 ± 0.05 IU/L, p = 0.004) and sFlt-1 (596.19 ± 283.06 vs. 436.53 ± 248.23 pg/L, p

PURPOSE: Despite studies focused on the association between embryo morphology and implantation potential, it is unknown how the collective quality of the supernumerary embryos in a cohort is associated with the implantation rate (IR) of the transferred embryo. This study tested the hypothesis that a relationship exists between the quality of the supernumerary cohort and IR. METHODS: A retrospective cohort study of first fresh autologous IVF cycles from 05/2012 to 09/2016, with ≥ 3 blastocysts, resulting in a single blastocyst transfer (n = 819) was performed. Cohorts were grouped in two ways: by mean priority score (PS; 1 being best) of supernumerary embryos and by percent supernumerary embryos with low implantation potential. The relationship between cohort quality and IR was assessed using logistic regression. RESULTS: As mean cohort PS increased, IR of the transferred embryo decreased (test for linear trend, p = 0.05). When ≥ 75% of the supernumerary cohort was predicted to have low implantation potential, IR of the transferred embryo was significantly lower compared to when

PURPOSE: Recent studies have shown that improved clinical outcomes can be achieved by transferring blastocysts rather than cleavage-stage embryos. However, blastocyst transfer is not performed in all patients. The aim of this study was to compare clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles using testicular sperm (TE) with those of ICSI cycles using ejaculated sperm (EJ). METHODS: ICSI was performed using EJ in 141 cycles and TE in 37 cycles. Embryos were cultured for 5 days. The quality of embryos was assessed on days 3 and 5 before embryo transfer. RESULTS: Fertilization rate was 77.3% in the EJ group and 69.6% in the TE group (p

The aim of the study was to evaluate two methods of endometrial preparation for frozen-thawed single euploid blastocyst transfer: modified natural and artificial cycle with GnRH-agonist pituitary suppression. In this prospective, controlled randomized trial, a total of 236 patients undergoing infertility treatment were randomized in 1:1 ratio; 118 received a frozen-thawed single euploid blastocyst transfer in a modified natural cycle and 118 in an artificial cycle with GnRH-agonist pituitary suppression. In the artificial protocol, GnRH-agonist combined with estradiol valerate was administered. In the natural protocol, only final oocyte maturation was induced using human chorionic gonadotropin administration. The primary end-points were the clinical pregnancy and implantation rates; the secondary end-points were the cost-benefit in terms of drug cost and the number of visits and the woman psychological distress caused by the treatment. No significant differences were found in clinical pregnancy, implantation, and miscarriage rates between protocols. The number of clinical and ultrasound controls and the number of laboratory dosages and venous samplings were similar in both study groups. No significant differences were found between the groups in the anxiety and depression values before the start of treatment, on the days of progesterone administration, the blastocyst transfer, and pregnancy test. The findings of this study evidence that in case of frozen-thawed single euploid blastocyst transfer, both protocols are equally effective in terms of clinical outcomes, cost-benefit, and patient compliance. The choice of endometrial preparation protocol should be based on women menstrual and ovulatory characteristics or otherwise on patient need for cycle planning. www.clinicaltrials.gov with number NCT02378584

The purpose of this study was to determine which morphokinetic variables are related to embryo gender in a cohort of consecutive live births obtained through single blastocyst transfer following mild ovarian stimulation. Eighty-one live births (49 % of them females) from successfully treated, consecutive infertile patients (maternal age 36.9 ± 3.8 years, range 28–46) who underwent minimal ovarian stimulation, prolonged embryo culture in a time-lapse monitoring (TLM) incubator and elective single blastocyst transfers during 2012–2014. Early (PNf, t2–t9, cc2a, b, s2, s3) and late (tM, tSB, tfullB, texpB1, and texpB2) morphokinetic variables were scored according to published consensus criteria and were normalized to the time of pronuclear fading. For each variable, the ranges with the highest proportion of female embryos (optimal range) were determined by detailed examination of histograms. Female embryo gender was associated both with late cleavage (t8), morula (tM), and blastocyst stage morphokinetic variables. The strongest associations (adjusted ORs, 7.0–7.8) were found for late, expanded stage blastocyst parameters; tfullB, texpB1, and texpB2. The proportion of female embryos was 69–71 and 25–26 % inside and outside of the optimal ranges, respectively. This allowed to predict 74–78 % of them, increasing their proportion by 57 % compared to the average. Although the sample size of our cohort was limited, our findings suggest that several expanded blastocyst stage morphokinetic parameters are associated with female embryo gender. If confirmed on a larger sample these could be potentially used to increase the proportion of female embryos among non-invasively selected blastocysts following single embryo transfer.

Prolonged in vitro culture is thought to affect pre- and postnatal development of the embryo. This prospective study was set up to determine whether quality/size of inner cell mass (ICM) (from which the fetus ultimately develops) and trophectoderm (TE) (from which the placenta ultimately develops) is reflected in birth and placental weight, healthy live-birth rate, and gender after fresh and frozen single blastocyst transfer. In 225 patients, qualitative scoring of blastocysts was done according to the criteria expansion, ICM, and TE appearance. In parallel, all three parameters were quantified semi-automatically. TE quality and cell number were the only parameters that predicted treatment outcome. In detail, pregnancies that continued on to a live birth could be distinguished from those pregnancies that aborted on the basis of TE grade and cell number. Male blastocysts had a 2.53 higher chance of showing TE of quality A compared to female ones. There was no correlation between the appearance of both cell lineages and birth or placental weight, respectively. The presented correlation of TE with outcome indicates that TE scoring could replace ICM scoring in terms of priority. This would automatically require a rethinking process in terms of blastocyst selection and cryopreservation strategy.

The answer to the question in the chapter subtitle depends very much on the knowledge of the examiner of placentas. From my perspective, perhaps the most interesting aspects have been the placental changes that are now being observed in multiple gestations and that result from the different practices of assisted reproductive technology (ART), in-vitro fertilization (IVF), and, especially, intracytoplasmic sperm injection (ICSI). The increased frequency with which excessive numbers of multiples are produced has been widely commented upon, and in recent publications it has been recommended that only single ovum transfers be practiced in ART, rather than the more frequent method of multiple blastocyst transfer. The attending prematurity rate and the frequently serious sequelae of marked prematurity have been the principal reasons for this recommendation. Additionally, because of uterine space limitations when multiple blastocysts compete for implantation sites, some placentas may become “squeezed” by the other placenta(s) and thus acquire less room for their expansion. This may then lead to fetal growth restriction and the more frequent and abnormal (velamentous) cord insertion seen in the placentas of multiples. We recently studied 127 sets of triplet placentas that had more single umbilical arteries (SUAs), more circumvallation, more chorangiomas, and, interestingly, more placentas with increased syncytial knots. More recently we saw a normal-appearing newborn with SUA who had a major contribution of cells that were mosaic for an 18q deletion. Thus one may ask, How normal are children with SUA?

International audience; Purpose While extended culture has been considerably improved, some questions remain regarding the application of Single Blastocyst Transfer (SBT). Methods An observational cohort study was undertaken with 456 women under 36 years old and assigned to SBT on a voluntary basis. The main outcome was the cumulative delivery rate per couple according to the number of Top Quality Embryos (TQE) on day 2 (Group 1= >= 2 TQE, Group 2= 1 TQE and Group 3= 0 TQE). Results Rate of transfer and mean number of frozen blastocyts were higher in Group 1 compared to Group 3. As a consequence, the cumulative delivery rate per couple was higher in Group 1 (47.9%) compared to Group 3 (34.9%). Conclusions Single blastocyst transfer combining fresh and frozen cycles, might be a worthwhile strategy irrespective of embryo quality on day 2 providing good delivery rates while keeping the rate of multiple deliveries low.

To investigate the difference in sex ratio in our centre after day 5 embryo transfer among neonates delivered after fresh in vitro fertilization (IVF), fresh intra cytoplasmatic sperminjection (ICSI) and frozen embryo replacement (FER) compared to expected sex ratio in normal population.Retrospective data after IVF/ICSI/FER therapy from 1995 - 2007 and data from the literature on similar subjects.Among a total of 420 births after day 5 transfer, there were 225 male and 195 female babies. However, after ICSI alone 30 were female and 21 male. Adding all available data from the literature on gender ratio after long term culture, the ratio of male births to total births (0.545) was significantly (p = 0.004) different from the expected ratio (0.515).It appears that significantly more males are born than expected after day 5 transfer in IVF. However, a subgroup analysis in our data comparing IVF, ICSI and FER revealed more females born after ICSI and FER, suggesting that further research is needed in this area.