Embryo Transfer In Patients Research Articles

P–428 Uterine infusion of autologous platelet rich plasma (PRP) before embryo transfer may improve the transfer outcomes in recurrent implantation failure and thin/scarred endometrium patients

Abstract Study question Does the infusion of autologous platelet rich plasma (PRP) to the uterus improve the outcomes of embryo transfer of thin endometrial or recurrent implantation failure (RIF) patients? Summary answer Autologous PRP uterine infusion may improve the result of embryo transfer (ET) in RIF group and thin/scarred endometrial group. What is known already Autologous PRP has been proposed to improve the outcomes of various treatment procedures. In infertility, several trials have reported an improvement in endometrial thickness in patients having thin endometrium thus previously cancelled ET cycles. Uterine injection of PRP shortly before ET has been proposed to improve the results of ET in patients having RIF. Platelets in PRP would be activated via different pathways to release growth factors and cytokines. In this study, we applied our in-house-developed PRP extraction kits that use a mechanical activation/platelet breaking down method to infuse/inject into the uterine of the poor prognosis transfer patients. Study design, size, duration This study includes two phases: Phase 1 (04/2019–12/2019): we tested the safety and effectiveness of the PRP extraction kits in 30 volunteers regardless of the gender by derma-rolling process using PRP extracted by our kits. Phase 2 (02/2020–12/2020): 111 IVF patients who had thin/scarred endometrium previously having at least one cancelled ET cycle (group 1) or patients who had at least two implantation failure ETs (group 2) were enrolled in the study. Participants/materials, setting, methods 20 mL blood was drawn from the vein. After centrifugation, PRP was filtrated through a filter to break down platelets releasing growth factors/cytokines. Firstly, 30 volunteers (average age of 34.4 ± 5.5) were derma-rolled on the facial skin twice (one week apart). Secondly, IVF group 1 was uterine-infused with 0.5 mL PRP on day 7/8 of the ET cycle, both groups were uterine-infused with 0.5 mL PRP two days (40–48 hours) before ET. Main results and the role of chance 0.5 mL of PRP before filtering was measured and calculated to have 8–12 folds increase of platelet concentration. In phase 1, no side-effects or complications were recorded. The average skin pore size reduced by approximately 0.01 mm2 in all patients two weeks after treatment. In phase 2, the average age was 35.6 ± 6.1. Group 1 had 31 patients and group 2 had 99 ones. In group 1, five patient did not obtained improvement in endometrium then ET cycles were cancelled, one patient did not have blastocyst to transfer and 25 patients had endometrium of at least 7 mm thick before ET and ET (100 frozen ET) were carried on. One couple was not contactable. Out of 24 couples, 13 had biochemical pregnancy (54.2%) and 11 had clinical pregnancy (44.0%). Group 2 had 80 patients. One of them did not have embryo to transfer. 37/79 embryo transfers had biochemical pregnancy (46.8%) and 44.3% clinical pregnancy. No complication was recorded. In our cohort, several successful patients had more than 7 unsuccessful ETs previously. For reference, in 2020, our clinic had 4260 ETs in total, the clinical pregnancy rate was 60.1%, the average age was 31.82 years old. Limitations, reasons for caution Each case in phase 2 of this study had a complicated fertility medical history therefore it was impossible to select the control group. This study is descriptive only. The size of each group was relatively small requiring ongoing data recording. Wider implications of the findings: This study support the idea that cytokines and growth factors in PRP may help to prepare endometrium for ET, safely and effectively. Trial registration number Not applicable

Administration of oxytocin antagonist at the same time as using a Foley catheter with cotton swab before embryo transfer for cervical stenosis

BackgroundEmbryo transfer without difficulty in a patient with cervical stenosis can be a great challenge for in vitro fertilization (IVF). We report a successful pregnancy following a frozen thawed embryo transfer after administration of an oxytocin antagonist at the same time as using a Foley catheter with cotton swab in a patient with refractory cervical stenosis.Case presentationA 40-year-old woman undergoing IVF. The patient’s previous embryo transfers were difficult. For every transfer, uterine manipulation was needed, force was required, and dilatation was necessary. A Foley catheter with a cotton swab was inserted into the cervical canal, atosiban was administered at the same time, and the Foley catheter was removed immediately before embryo transfer. A smooth transfer was performed without bleeding, force, uterine manipulation, or cervical dilator. The patient became pregnant and delivered by cesarean section at term.ConclusionThis method is effective in performing atraumatic embryo transfer in patients with cervical stenosis.

Associations of FSHR and LHCGR gene variants with ovarian reserve and clinical pregnancy rates

Research questionAre there any associations between the variants of FSHR c.2039 G>A (p. Ser680Asn, rs6166) and LHCGR c.935A>G (p. Asn312Ser, rs2293275) and ovarian reserve, ovarian response, clinical pregnancy rate and POSEIDON group? DesignA total of 210 infertile women were enrolled in this prospective study. The gene variants were analysed by the Sanger method. The clinical parameters were analysed based on genotypes. ResultsThe frequency of heterozygous and homozygous G allele for FSHR c.2039 G>A in the low prognosis group was significantly higher than that in other response groups (P = 0.034); there was no significant association between LHCGR c.935 A>G and ovarian response. Moreover, the serum anti-Müllerian hormone (AMH) concentration, antral follicle count (AFC), oocytes retrieved, metaphase II (MII) oocytes and two-pronuclear (2PN) oocytes in patients with AG genotype for FSHR c.2039 G>A were significantly lower than those with AA genotype. The serum LH concentrations and clinical pregnancy rate of fresh embryo transfer in patients with GG genotype for LHCGR c.935 A>G were significantly higher than that of the AG genotype. In POSEIDON analysis, the low prognosis women with AA genotype for FSHR c.2039 G>A were more likely to appear in subgroup 1 (P = 0.038). ConclusionThe FSHR c.2039 G>A variant has a significant beneficial influence on ovarian reserve and ovarian response. The LHCGR c.935 A>G variant is associated with increased clinical pregnancy rate of fresh embryo transfer in infertile women. In addition, the low prognosis women with AA genotype for FSHR c.2039 G>A tend to show better ovarian reserve and prognosis.

Is frozen embryo transfer better than fresh embryo transfer in women undergoing intracytoplasmic sperm injection over the age of thirty-five? A single referral centre experience

Developments in embryo freezing techniques in recent years have increased the chance of pregnancy after frozen embryo transfers. In this study we aimed to compare the pregnancy outcomes between fresh (ET) and frozen-thawed embryo transfer (FET) and to evaluate the benefits of embryo freezing strategy for a woman of advanced age. A total of 513 ET cycles in women over the age of 35 years, including 397 fresh ET cycles and 116 FET cycles were reviewed. Mean age was 37.7 ± 2.91 years in FET cycles and 38 ± 2.8 in fresh cycles (p = .327). The patients undergoing FET cycles had higher oestradiol levels and progesterone levels on the day of trigger in their previous fresh cycles compared to that of fresh ET cycles (1675 pmol/L versus 991 pmol/L; 1.43 pmol/L versus 0.96 pmol/L; p < .005, respectively). Biochemical pregnancy rates (43% versus 32%; p = .048), clinical pregnancy rates (38% versus 29%; p = .030) and live birth rates (30% versus 19.6%; p = .013) were significantly higher in the FET than in the fresh ET over 35 years of age. IMPACT STATEMENT What is alreday known on this subject? Ovarian stimulation commonly results in the generation of more embryos than are necessary for the fresh embryo transfer. Therefore, cryopreservation and subsequent replacement of frozen–thawed embryos is an integral part of assisted reproductive technique (ART) programs. As IVF technology improved, embryo freezing was performed to allow subsequent transfer if the fresh cycle was unsuccessful. What do the results of this study add? Clinical pregnancy rates and live birth rates were found to be higher in frozen thawed embryo transfer group compared to fresh embryo transfer group over the age of 35. What are the implications of these findings for clinical practice and/or further research? Frozen thawed embryo transfer seems to be a reasonable and favourable method compared to fresh embryo transfer in patients over 35 years.

Effect of body mass index on the assisted reproductive outcome of frozen-thawed embryo transfer in patients with polycystic ovary syndrome

Objective: To investigate the effect of body mass index (BMI) on clinical pregnancy and neonatal outcomes in patients with polycystic ovary syndrome (PCOS) during frozen-thawed embryo transfer. Methods: A total of 650 patients with PCOS who received routine in vitro fertilization or intracytoplasmic sperm injection treatment for frozen-thawed embryo transfer from June 2014 to June 2019 in Tianjin Central Hospital of Gynecology Obstetrics were retrospectively analyzed. According to BMI, PCOS patients were divided into group A (18.5≤BMI<23 kg/m2, n=253), group B (23≤BMI<25 kg/m2, n=167), and group C (BMI≥25 kg/m2, n=230). The general information, clinical pregnancy outcomes, pregnancy complications, the incidence of macrosomia and low-birth-weight infants were compared in the three groups, and the influencing factors of neonatal birth weight were analyzed. Results: The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate all showed downward trend with the increase of BMI, but the differences were not statistically significant (all P>0.05). The live birth rate in group C [47.0% (108/230)] was significantly lower than those in groups A and B, with statistical significance (χ²=7.43, P=0.024). The late miscarriage rate was higher in group C [9.4% (13/139)] than in groups A and B (χ²=7.66, P=0.022). The birth rates of macrosomia in groups B [22.2% (16/72)] and group C [21.1% (16/76)] were significantly higher than that in group A, and the difference was statistically significant (χ²=14.15, P=0.001). There was no statistically significant difference in the incidence of gestational diabetes between the three groups (χ²=3.81, P=0.149). The incidence of hypertension disorders complicating pregnancy increased with the increase of BMI, and the difference was not statistically significant (P>0.05). Regression analysis showed that macrosomia was significantly associated with maternal pre-pregnancy BMI and gestational weeks, and the risk of macrosomia increased by 15% (95%CI: 3%-28%) for every increase in maternal BMI. Conclusions: The embryo implantation rate, clinical pregnancy rate, and ongoing pregnancy rate of PCOS patients in frozen-thawed embryo transfer cycles show downward trend with the increase of BMI. Obese patients with PCOS have a significant increase in late miscarriage rate and a significant decrease in live birth rate. The incidence of hypertension disorders complicating pregnancy in PCOS patients in the obese group has an increasing trend, and the birth rate of macrosomia has increased significantly. Therefore, it is recommended that obese women with PCOS lose weight scientifically before pregnancy to improve pregnancy and neonatal outcomes.

Immediate versus delayed frozen embryo transfer in patients following a stimulated IVF cycle: a randomised controlled trial.

Is there any difference in the ongoing pregnancy rate after immediate versus delayed frozen embryo transfer (FET) following a stimulated IVF cycle? Immediate FET following a stimulated IVF cycle produced significantly higher ongoing pregnancy and live birth rate than did delayed FET. Embryo cryopreservation is an increasingly important part of IVF, but there is still no good evidence to advise when to perform FET following a stimulated IVF cycle. All published studies are retrospective, and the findings are contradictory. This was a randomised controlled non-inferiority trial of 724 infertile women carried out in two fertility centres in China between 9 August 2017 and 5 December 2018. Infertile women having their first FET cycle after a stimulated IVF cycle were randomly assigned to either (1) the immediate group in which FET was performed in the first menstrual cycle following the stimulated IVF cycle (n = 362) or (2) the delayed group in which FET was performed in the second or later menstrual cycle following the stimulated IVF cycle (n = 362). All FET cycles were performed in hormone replacement cycles. The randomisation sequence was generated using an online randomisation program with block sizes of four. The primary outcome was the ongoing pregnancy rate, defined as a viable pregnancy beyond 12 weeks of gestation. The non-inferiority margin was -10%. Analysis was performed by both per-protocol and intention-to-treat approaches. Women in the immediate group were slightly younger than those in the delayed group (30.0 (27.7-33.5) versus 31.0 (28.5-34.2), respectively, P = 0.006), but the proportion of women ≤35 years was comparable between the two groups (308/362, 85.1% in the immediate group versus 303/362, 83.7% in the delayed group). The ongoing pregnancy rate was 49.6% (171/345) in the immediate group and 41.5% (142/342) in the delayed group (odds ratios 0.72, 95% CI 0.53-0.98, P = 0.034). The live birth rate was 47.2% (163/345) in the immediate group and 37.7% (129/342) in the delayed group (odds ratios 0.68, 95% CI 0.50-0.92, P = 0.012). The miscarriage rate was 13.2% (26 of 197 women) in the immediate group and 24.2% (43 of 178 women) in the delayed group (odds ratios 2.10; 95% CI 1.23-3.58, P = 0.006). The multivariable logistic regression, which adjusted for potential confounding factors including maternal age, number of oocytes retrieved, embryo stage at transfer, number of transferred embryos/blastocysts, reasons for FET, ovarian stimulation protocol and trigger type, demonstrated that the ongoing pregnancy rate was still higher in the immediate group. Despite randomisation, the two groups still differed slightly in the age of the women at IVF. The study was powered to consider the ongoing pregnancy rate, but the live birth rate may be of greater clinical interest. Conclusions relating to the observed differences between the treatment groups in terms of live birth rate should, therefore, be made with caution. Immediate FET following a stimulated IVF cycle had a significantly higher ongoing pregnancy and live birth rate than delayed FET. The findings of this study support immediate FET after a stimulated IVF cycle. No external funding was used and no competing interests were declared. ClinicalTials.gov identifier: NCT03201783. 28 June 2017. 9 August 2017.

Spectroscopy analysis of endometrial metabolites is a powerful predictor of success of embryo transfer in women with implantation failure: a preliminary study

Objective To investigate whether prior endometrium spectroscopy predicts the success of embryo transfer in patients with recurrent implantation failure (RIF). Materials and methods Twenty women with RIF who were scheduled for IVF-ET and six fertile women were included the study. All women with RIF and fertile controls underwent endometrium spectroscopy before embryo transfer. A multi-voxel spectroscopy sequence was used for the detection of choline (Cho), creatine (Cr), lactate, and lipids. Women with RIF were divided into two subgroups as successful (n = 8) and unsuccessful RIF (n = 12) according to both Cho and Cr metabolite characteristics and whether pregnancy was achieved. Associations between the metabolite intensities of the RIF subjects and the implantation rate (IR) and clinical pregnancy rate (CPR) were assessed. Results While 8 of 20 RIF cases became pregnant, pregnancy could not be achieved in 12 cases. The common spectroscopy finding in all 8 cases who conceived was high Cho and low lactate. The main metabolite change detected in 12 patients who could not conceive was the increase in lactate and lipid signals. The cutoff value of Cho, Cr, lactate and lipid were 1.01 ppm, 1.44 ppm, 0.86 ppm and 1.22 ppm respectively in patients who achieved pregnancy following ET. A positive and significant correlation was found between Cho and Cr intensities and IR or CPR. Conclusions Receptive endometrium represents some specific metabolites in spectroscopy that can be used for prediction of the success or failure of embryo transfer in women suffering implantation failure.

Impact of previous cesarean delivery on pregnancy outcomes of in vitro fertilization and frozen-thawed embryo transfer

Objective: To investigate the impact of a previous cesarean delivery on pregnancy outcomes of in vitro fertilization and frozen-thawed embryo transfer (FET). Methods: The clinical data of 1 179 patients who received in vitro fertilization and FET in Tianjin Central Hospital of Gynecology Obstetrics from January 2014 to May 2019 and had a history of the previous delivery were retrospectively analyzed. The patients were divided into four groups according to different previous delivery history and the number of embryo transferred: group A (single embryo transfer group with cesarean delivery history, n=338), group B (single embryo transfer group with vaginal delivery history, n=78), group C (double embryo transfer group with cesarean delivery history, n=444), and group D (double embryo transfer group with vaginal delivery history, n=319). The 1∶1 propensity score based on age, body mass index (BMI), infertility duration, basal FSH, basal LH, number of oocytes retrieved and high-quality embryo rate was used to match group A and B (caliper value=0.15), group C and D (caliper value=0.05), and group A and C (caliper value=0.01) respectively to reduce the influence of selection bias. The clinical pregnancy outcomes of patients were compared. Results: (1) Group A and group B were single embryo transfer groups with a total of 77 pairs of matched patients. There were no statistically significant differences in clinical pregnancy rate [42.9% (33/77) vs 45.5% (35/77)], miscarriage rate, preterm birth rate, and neonatal birth weight (all P>0.05). (2) Group C and group D were double embryo transfer groups with a total of 304 pairs of matched patients. The clinical pregnancy rate [42.4% (129/304)] and twin pregnancy rate [9.5% (29/304)] of Group C were significantly lower than those of Group D [53.0% (161/304), 15.5% (47/304) respectively; both P<0.05). There were no statistically significant in miscarriage rate, preterm birth rate and neonatal birth weight between the two groups (all P>0.05). (3) Groups A and C matched 318 pairs of patients. The two groups had no statistical significances in clinical pregnancy rate [38.4% (122/318) vs 45.6% (145/318)], miscarriage rate and preterm birth rate (all P>0.05), but the twin pregnancy rate in group C was significantly higher than that of group A [11.3% (36/318) vs 0.3% (1/318), P<0.01). (4) The occurrence of the low-birth-weight infant were related to gestational age (OR=0.41, 95%CI: 0.32-0.54) and twin pregnancy (OR=4.44, 95%CI: 1.93-10.21), and the occurrence of macrosomia was related to BMI (OR=1.18, 95%CI: 1.06-1.32). Moreover, the previous delivery method was not related to the neonatal birth weight (P>0.05). Conclusions: Patients with different delivery histories receive FET therapy, the pregnancy outcomes of single embryo transfer are not significantly different, and the success rate of double embryo transfer in patients with a cesarean delivery history is low. The neonatal birth weight is not related to the history of the cesarean section. It is recommended that patients with a cesarean delivery history choose elective single embryo transfer to ensure the success rate and to reduce the risk.

Stimulated cycle versus artificial cycle for frozen embryo transfer in patients with polycystic ovary syndrome: a Meta-analysis

Purpose Our aim is to conduct a meta-analysis comparing clinical outcomes between the mild ovarian stimulation cycle versus an artificial cycle (AC) for frozen embryo transfer (FET) in patients with polycystic ovary syndrome (PCOS). Methods We systematically searched the databases of PubMed, EMBASE and the Cochrane Library from inception to January 2020. The outcomes were live birth rate (LBR), ongoing pregnancy rate (OPR), clinical pregnancy rate (CPR), embryo implantation rate (IR) and miscarriage rate (MR). The mild ovarian stimulation cycle and AC were compared according to risk ratios and 95% confidence intervals using a fixed or random effects model. Results Four retrospective studies describing the clinical outcomes were included. We found no significant difference in LBR, OPR, CPR, IR or MR between the mild ovarian stimulation cycle and AC protocols, whereas a lower MR was found for the letrozole-stimulated cycle than the AC. Conclusions The letrozole-stimulated cycle for endometrial preparation in PCOS patients undergoing FET may lower the MR more than the AC. PCOS patients using the mild ovarian stimulation cycle for endometrial preparation undergoing FET had similar LBR, OPR, CPR and IR compared with the AC. The letrozole-stimulated protocol may be a reasonable choice for endometrial preparation before FET for women with PCOS.

Эффективность программ криопереноса в зависимости от транскрипционного «портрета» генов рецептивности эндометрия

Эффективность программ криопереноса в зависимости от транскрипционного «портрета» генов рецептивности эндометрия

Uterine bathing with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis, a multicentre randomised controlled trial.

STUDY QUESTIONWhat is the effect of uterine bathing with sonography gel prior to IVF/ICSI-treatment on live birth rates after fresh embryo transfer in patients with endometriosis?SUMMARY ANSWERAfter formal interim analysis and premature ending of the trial, no significant difference between uterine bathing using a pharmacologically neutral sonography gel compared to a sham procedure on live birth rate after fresh embryo transfer in endometriosis patients (26.7% vs. 15.4%, relative risk (RR) 1.73, 95% confidence interval (CI) 0.81–3.72; P-value 0.147) could be found, although the trial was underpowered to draw definite conclusions.WHAT IS KNOWN ALREADYImpaired implantation receptivity contributes to reduced clinical pregnancy rates after IVF/ICSI-treatment in endometriosis patients. Previous studies have suggested a favourable effect of tubal flushing with Lipiodol® on natural conceptions. This benefit might also be explained by enhancing implantation through endometrial immunomodulation. Although recent studies showed no beneficial effect of endometrial scratching, the effect of mechanical stress by intrauterine infusion on the endometrium in endometriosis patients undergoing IVF/ICSI-treatment has not been investigated yet.STUDY DESIGN, SIZE, DURATIONWe performed a multicentre, patient-blinded, randomised controlled trial in which women were randomly allocated to either a Gel Infusion Sonography (GIS, intervention group) or a sham procedure (control group) prior to IVF/ICSI-treatment. Since recruitment was slow and completion of the study was considered unfeasible, the study was halted after inclusion of 112 of the planned 184 women.PARTICIPANTS/MATERIALS, SETTING, METHODSWe included infertile women with surgically confirmed endometriosis ASRM stage I–IV undergoing IVF/ICSI-treatment. After informed consent, women were randomised to GIS with intrauterine instillation of ExEm-gel® or sonography with gel into the vagina (sham). This was performed in the cycle preceding the embryo transfer, on the day GnRH analogue treatment was started. The primary endpoint was live birth rate after fresh embryo transfer. Analysis was performed by both intention-to-treat and per-protocol.MAIN RESULTS AND THE ROLE OF CHANCEBetween July 2014 to September 2018, we randomly allocated 112 women to GIS (n = 60) or sham procedure (n = 52). The live birth rate after fresh embryo transfer was 16/60 (26.7%) after GIS versus 8/52 (15.4%) after the sham (RR 1.73, 95% CI 0.81–3.72; P-value 0.147). Ongoing pregnancy rate was 16/60 (26.7%) after GIS versus 9/52 (17.3%) in the controls (RR 1.54, 95% CI 0.74–3.18). Miscarriage occurred in 1/60 (1.7%) after GIS versus 5/52 (9.6%) in the controls (RR 0.17, 95% CI 0.02–1.44) women. Uterine bathing resulted in a higher pain score compared with a sham procedure (visual analogue scale score 2.7 [1.3–3.5] vs. 1.0 [0.0–2.0], P < 0.001). There were two adverse events after GIS compared with none after sham procedures.LIMITATIONS, REASONS FOR CAUTIONThe study was terminated prematurely due to slow recruitment and trial fatigue. Therefore, the trial is underpowered to draw definite conclusions regarding the effect of uterine bathing with sonography gel on live birth rate after fresh embryo transfer in endometriosis patients undergoing IVF/ICSI-treatment.WIDER IMPLICATIONS OF THE FINDINGSWe could not demonstrate a favourable effect of uterine bathing procedures with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis.STUDY FUNDING/COMPETING INTEREST(S)Investigator initiated study. IQ Medical Ventures provided the ExEm FOAM® kits free of charge, they were not involved in the study design, data management, statistical analyses and/or manuscript preparation, etc. C.B.L. reports receiving grants from Ferring, Merck and Guerbet, outside the submitted work. C.B.L. is Editor-in-Chief of Human Reproduction. V.M. reports grants and other from Guerbet, outside the submitted work. B.W.M. reports grants from NHMRC (GNT1176437), personal fees from ObsEva, Merck and Merck KGaA, Guerbet and iGenomix, outside the submitted work. N.P.J. reports research funding from Abb-Vie and Myovant Sciences and consultancy for Vifor Pharma, Guerbet, Myovant Sciences and Roche Diagnostics, outside the submitted work. K.D. reports personal fees from Guerbet, outside the submitted work. The other authors do not report any conflicts of interest. No financial support was provided.TRIAL REGISTRATION NUMBERNL4025 (NTR4198)TRIAL REGISTRATION DATE7 October 2013DATE OF FIRST PATIENT’S ENROLMENT22 July 2014

Clinical value of histologic endometrial dating for personalized frozen-thawed embryo transfer in patients with repeated implantation failure in natural cycles

BackgroundDisplacement of the window of implantation (WOI) has been proposed as an important factor contributing to repeated implantation failure (RIF). However, the use of histologic endometrial dating as a diagnostic tool of endometrial receptivity has been questioned.MethodsThis study is a prospective intervention trial that enrolled 205 infertile patients from July 2017 to December 2017. Endometrial biopsies from 50 patients with good prognoses were conducted on day 3 (n = 6), 5 (n = 6), 7 (n = 26), 9 (n = 6), or 11 (n = 6) post-ovulation (PO + 3/5/7/9/11) of the previous natural cycle before their conventional frozen-thawed embryo transfer (FET) cycle. We conducted endometrial biopsies for 155 RIF patients on day PO + 7.ResultsThe verification of the Noyes criteria for endometrial dating was conducted at different times (PO + 3/+ 5/+ 7/+ 9/+ 11) on 41 patients with good prognoses who achieved an ongoing pregnancy in their first conventional FET cycle after endometrial biopsy. The agreement between two pathologists determining endometrial biopsy dating results in infertile patients was determined to be acceptable (weighted kappa = 0.672, P < 0.001). The rate of out-of-phase dating on day PO + 7 was significantly higher in RIF patients than in good- prognosis patients (31.6% vs. 3.8%, P = 0.003). pFET was performed in 47 RIF patients diagnosed to be out of phase, and the cumulative live-birth rate was 61.7%.ConclusionsHistologic endometrial dating of RIF patients in natural cycles may be a biomarker for a receptive endometrium in diagnosing WOI displacement.Trial registrationNCT03312309 Registered 17 October 2017.NCT03222830 Registered 19 July 2017,

The intrauterine perfusion of granulocyte-colony stimulating factor (G-CSF) before frozen-thawed embryo transfer in patients with two or more implantation failures

The objective of this study was to investigate the clinical benefits of intrauterine perfusion with G-CSF in patients undergoing a frozen-thawed embryo transfer (FET) after at least two previous implantation failures. This was a prospective, randomized, single-blind study. The intervention group received an intrauterine infusion of G-CSF whereas the placebo group was given an intrauterine infusion of physiological saline before embryo transfer. A third (control) group did not receive an intrauterine infusion prior to embryo transfer. The clinical pregnancy rates of both the intervention and placebo group were significantly higher than that in the control group (p < 0.05). But the miscarriage rates of the G-CSF were significantly lower than those of the other two groups (p < 0.05). The intrauterine infusion of G-CSF before frozen-thawed embryo transfer significantly reduced miscarriage rates and improve the live birth rates. While intrauterine perfusion with physiological saline did not reduce miscarriage rates.

Analysis of the guidance value of 3D ultrasound in evaluating endometrial receptivity for frozen-thawed embryo transfer in patients with repeated implantation failure.

BackgroundRepeated implantation failure (RIF) is currently believed by some scholars to be mainly related to the poor endometrial receptivity. Three-dimensional (3D) ultrasound, as a noninvasive examination, has attracted the most attention. This paper further discusses whether 3D ultrasound of the endometrial receptivity index has guidance value in the evaluation of pregnancy outcomes in patients with RIF following frozen-thawed embryo transfer.MethodsA total of 79 patients with RIF were retrospectively analyzed. These 79 patients which were confirmed by the transvaginal ultrasonography detection comprised 36 cases of intrauterine pregnancy, which were included in the pregnancy group, and 43 cases with biochemical pregnancy (the HCG in blood or urine is only transient and can be detected by clinical biochemical methods. The pregnancy sac cannot be seen under ultrasound) or negative results of human chorionic gonadotropin (HCG) examination, which were included in the non-pregnancy group. The endometrial thickness, uterine volume, sub-endometrial blood flow type, pulsatility index (PI) and resistance index (RI) of the spiral artery; the RI and PI of the uterine artery; and the peak systolic velocity/end diastolic velocity (S/D) of the two groups were measured and analyzed.Results(I) There were no significant differences in the age, infertility years, body mass index (BMI), anti-Müllerian hormone (AMH), endometrial thickness on the hCG injection day, estradiol (E2), and progesterone (P) between the pregnant and non-pregnant groups (P>0.05). (II) There were no significant differences in the endometrial thickness, uterine volume, and RI and PI of the uterine artery on the day before the implantation between the two groups (P>0.05). (III) There was statistical difference in the sum of the S/D of the two uterine arteries between the two groups (P<0.05) with a cutoff value of 14.47 (P<0.05). (IV) The RI and PI of the spiral artery in the non-pregnancy group were lower than those in the pregnancy group, and the difference was statistically significant (P<0.05). (V) The differences in the endometrial classification and subendometrial blood flow classification between the two groups were statistically significant (P<0.05).ConclusionsUltrasonographic endometrial blood flow classification, spiral artery blood flow parameters, and uterine artery blood flow parameters can be effective indexes for evaluating endometrial receptivity, and they have a certain clinical significance in evaluating the pregnancy outcome of RIF patients after retransplantation.

Preimplantation genetic testing for aneuploidy in patients with partial X monosomy using their own oocytes: is this a suitable indication?

To describe the outcome of preimplantation genetic testing (PGT-A) using their own oocytes in patients with mosaic Turner Syndrome (MTS). The impact of the assisted reproduction technique (ART) performed (PGT-A or oocyte donation) and the type of absence of the X chromosome (total or partial) were considered. Retrospective observational multicenter study. University-affiliated private invitro fertilization center. Fifty-six patients with MTS with whom 65 ovarian stimulation cycles for PGT-A (fluorescence in situ hybridization/arrays-next generation sequencing) were performed. The study included 90 women with MTS and 20 women with pure Turner Syndrome (PTS) who underwent 140 and 25 oocyte donation (OD) cycles, respectively. Invitro fertilization for PGT-A (fluorescence in situ hybridization/arrays-next generation sequencing) or OD. Reproductive outcome and feto-maternal outcomes. The live birth rate (LBR) per embryo transfer in patients with MTS tended to be higher in OD 37.7% (95% confidence interval [CI]: 29.3-46.1) than that observed for PGT-A 22.5% (95% CI 7.8-38.2), and the cumulative LBR (CLBR), with 77.6% vs. 43.3%, respectively. Likewise, the LBR per patient was significant when comparing PGT-A vs. OD, with 12.5% (95 CI 3.9-21.1) vs. 51.1% (40.7-61.4), respectively. While focusing on the X chromosome, partial MTS (PTS), we found significant differences in the CLBR per embryo transfer, with 77.6% vs. 29.2%, and also in the LBR per patient: 51.1% (40.7-61.4) in MTS vs. 15% (95 CI 0.0-30.1) in PTS. Oocyte donation is the best reproductive option in females with Turner Syndrome with or without mosaicisms. Nevertheless, PGT-A is a valid therapeutic option in patients with MTS using their own oocytes, and OD should not necessarily be directly recommended.

Prognostic value of blastocyst grade after frozen euploid embryo transfer in patients with recurrent pregnancy loss

ObjectiveTo determine whether trophectoderm (TE) grade or inner cell mass (ICM) grade have predictive value after euploid frozen embryo transfer (euFET) among recurrent pregnancy loss (RPL) patients.DesignRetrospective cohort study.SettingSingle fertility center.Patient(s)Women with ≥2 prior pregnancy losses with ≥1 euploid embryo for transfer undergoing preimplantation genetic testing for aneuploidy.Intervention(s)Intracytoplasmic sperm injection, TE biopsy, blastocyst grading and vitrification, and single euFET, with first transfer outcome recorded.Main Outcome Measure(s)Live birth and clinical miscarriage rates.Result(s)The study included 660 euFET cycles. In a binomial logistic regression analysis accounting for age, body mass index, antimüllerian hormone level, and day of blastocyst biopsy, or ICM grade C was not significantly associated with odds of live birth, miscarriage, or biochemical pregnancy loss. TE grade C was significantly associated with odds of live birth and was not associated with odds of miscarriage or biochemical pregnancy loss. Blastocyst grade CC had significantly lower live birth rate compared with all other blastocyst grades.Conclusion(s)Embryo grade CC and TE grade C are associated with decreased odds of live birth after euFET in RPL patients. Embryo grade is not associated with odds of clinical miscarriage in this cohort of RPL patients, suggesting that additional embryonic or uterine factors may influence the risk of pregnancy loss.

Low progesterone levels on the day before natural cycle frozen embryo transfer are negatively associated with live birth rates.

Are progesterone (P) levels on the day before natural cycle frozen embryo transfer (NC-FET) associated with live birth rate (LBR)? Regular ovulatory women undergoing NC-FET with serum P levels <10 ng/ml on the day before blastocyst transfer have a significantly lower LBR than those with serum P levels >10 ng/ml. The importance of serum P levels around the time of embryo transfer in patients undergoing FET under artificial endometrial preparation has been well established. However, no study has analyzed the importance of serum P levels in patients undergoing FET under a true natural endometrial preparation cycle. This was a retrospective cohort study including 294 frozen blastocyst transfers under natural cycle endometrial preparation at a university-affiliated fertility centre between January 2016 and January 2019. All patients had regular menstrual cycles and underwent NC-FET with their own oocytes. Only patients who had undergone serum P measurement between 8 am and 11 am on the day before FET were included. Patients did not receive any external medication for endometrial preparation or luteal phase support. Patients were divided into two groups according to serum P levels below or above 10 ng/ml on the day before FET. Univariate analysis was carried out to describe and compare the cycle characteristics with reproductive outcomes. To evaluate the effect of P, a multivariable logistic model was fitted for each outcome after adjusting for confounding variables. Mean serum P levels on the day before FET were significantly higher in patients who had a live birth compared to those who did not (14.5 ± 7.0 vs 12.0 ± 6.6 ng/ml, 95% CI [0.83; 4.12]). The overall clinical pregnancy rate (CPR) and LBR were 42.9% and 35.4%, respectively. Patients in the higher P group (>10 ng/ml) had a higher LBR (41.1% vs 25.7%: risk difference (RD) 15.4%, 95% CI [5; 26]) and CPR (48.6% vs 33.0%: RD 15.6%, 95% CI [4; 27]). Patients with higher serum P levels on the day before FET (63% of patients) had an improved LBR (odds ratio: 1.05; 95% CI [1.02; 1.09]). Women with serum P levels <10 ng/ml on the day before FET (37% of patients) had significantly higher weights (62.5 ± 9.9 vs 58.1 ± 7.1 kg, 95% CI [1.92; 6.90]) and BMI (22.9 ± 3.6 vs 21.6 ± 2.7 kg/m2, 95% CI [0.42; 2.25]) compared to patients with P levels >10 ng/ml. The main limitation of our study is its retrospective design. Other potential limitations are the detection of LH surge through urine testing and the inclusion of patients who did and did not undergo preimplantation genetic testing for aneuploidies. The protocol used in our institution for monitoring NC-FET does not look for the onset of progesterone secretion by the corpus luteum, and a slow luteinisation process or delay of corpus luteum function cannot be ruled out. We provide evidence that a minimum serum P threshold (P >10 ng/ml) might be required for improved reproductive outcomes in NC-FET. This result suggests that there are different mechanisms by which P is produced and/or distributed by each patient. This study also provides an excellent model to evaluate the impact of luteal phase defect through NC-FET. A prospective evaluation to assess whether P supplementation should be individualised according to patient's needs is necessary to support our findings. No external funding was used, and there are no competing interests.

Analysis of efficiency of application of media with hyaluronic acid in cryoprotocols

According to the World Health Organization, about 2 million new couples experience infertility annually, and their number is growing. An effective way to overcome infertility is assisted reproductive technology (ART). Cryopreservation will rationally solve the issue of preservation and further use of embryos: to delay pregnancy for some time considering womans desire and to prevent ovarian hyperstimulation syndrome. Embryo freezing allows to reduce the rate of repeated ovarian stimulation and perform preimplantation genetic diagnosis. Over the past decades, various cryotransfer options have been proposed to increase ART treatment efficacy, including the use of a culture medium with a high concentration of hyaluronic acid, but there are conflicting data on the use of such a medium in ART programs.&#x0D; Aim. Evaluation of thawed embryo transfers efficacy using the hyaluronic acid-containing culture medium. To achieve the goal, the following tasks were set: to evaluate clinical and medical history data of patients with tubal infertility in cryoprotocols, to analyze the previous cycle of in vitro fertilization and embryological stage, to evaluate the effectiveness of the culture medium with a high content of hyaluronic acid.&#x0D; Materials and methods. A detailed description of the patient sample, inclusion and exclusion criteria, embryological stage, embryo grading, devitrified embryo transfer technique. The article includes 3 tables which present the groups general clinical characteristics, the embryological stage, the rate of pregnancy, depending on the cultivation day.&#x0D; Results. The authors established that in patients with a history of pelvic surgery and sexually transmitted infections, it is advisable to use the culture medium with a high content of hyaluronic acid to transfer the thawed embryo. It was shown that pregnancy rate is 1.5 times higher when transferring devitrified embryos on the 5th day of development with the use of hyaluronic acid-containing culture medium.&#x0D; The conclusion about the pregnancy rate in obese patients is not indisputable, which requires further study. The authors also provide practical recommendations on the use of the culture medium with hyaluronic acid in cryoprotocols.&#x0D; Conclusion. The study allows to optimize the devitrified embryo transfer in patients with tubal infertility using a culture medium with a high content of hyaluronan. This work has undoubted scientific and practical significance.

A decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for ovarian hyperstimulation syndrome after triggering final oocyte maturation with hCG.

STUDY QUESTIONCan the grade of ascites, haematocrit (Ht), white blood cell (WBC) count and maximal ovarian diameter (MOD) measured on Day 3 be used to construct a decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for severe ovarian hyperstimulation syndrome (OHSS) after an hCG trigger?SUMMARY ANSWERUsing cut-offs of ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm on Day 3, a decision-making algorithm was constructed that could predict subsequent development of severe OHSS on Day 5 with an AUC of 0.93, a sensitivity of 88.5% and a specificity of 84.2% in high-risk patients triggered with hCG.WHAT IS KNOWN ALREADYDespite the increasing popularity of GnRH agonist trigger for final oocyte maturation as a way to prevent OHSS, ≥75% of IVF cycles still involve an hCG trigger. Numerous risk factors and predictive models of OHSS have been proposed, but the measurement of these early predictors is restricted either prior to or during the controlled ovarian stimulation. In high-risk patients triggered with hCG, the identification of luteal-phase predictors assessed post-oocyte retrieval, which reflect the pathophysiological changes leading to severe early OHSS, is currently lacking.STUDY DESIGN, SIZE, DURATIONA retrospective study of 321 patients at high risk for severe OHSS following hCG triggering of final oocyte maturation. High risk for OHSS was defined as the presence of at least 19 follicles ≥11 mm on the day of triggering of final oocyte maturation.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study includes IVF/ICSI patients at high risk for developing severe OHSS, who administered hCG to trigger final oocyte maturation. Ascites grade, MOD, Ht and WBC were assessed in the luteal phase starting from the day of oocyte retrieval. Outcome measures were the optimal thresholds of ascites grade, MOD, Ht and WBC measured on Day 3 post-oocyte retrieval to predict subsequent severe OHSS development on Day 5. These criteria were used to construct a decision-making algorithm for embryo transfer, based on the estimated probability of severe OHSS development on Day 5.MAIN RESULTS AND THE ROLE OF CHANCEThe optimal Day 3 cutoffs for severe OHSS prediction on Day 5 were ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm. The probability of severe OHSS with no criteria fulfilled on Day 3 is 0% (95% CI: 0–5.5); with one criterion, 0.8% (95% CI: 0.15–4.6); with two criteria, 13.3% (95% CI: 7.4–22.8); with three criteria, 37.2% (95% CI: 24.4–52.1); and with four criteria, 88.9% (95% CI, 67.2–98.1). The predictive model of severe OHSS had an AUC of 0.93 with a sensitivity of 88.5% and a specificity of 84.2%.LIMITATIONS, REASONS FOR CAUTIONThis is a retrospective study, and therefore, it cannot be excluded that non-apparent sources of bias might be present. In addition, we acknowledge the lack of external validation of our model. We have created a web-based calculator (http://ohsspredict.org), for wider access and usage of our tool. By inserting the values of ascites grade, MOD, Ht and WBC of high-risk patients on Day 3 after oocyte retrieval, the clinician instantly receives the predicted probability of severe OHSS development on Day 5.WIDER IMPLICATIONS OF THE FINDINGSThe present study describes a novel decision-making algorithm for embryo transfer based on ascites, Ht, WBC and MOD measurements on Day 3. The algorithm may be useful for the management of high-risk patients triggered with hCG and for helping the clinician’s decision to proceed with, or to cancel, embryo transfer. It must be emphasized that the availability of the present decision-making algorithm should in no way encourage the use of hCG trigger in patients at high risk for OHSS. In these patients, the recommended approach is the use of GnRH antagonist protocols, GnRH agonist trigger and elective embryo cryopreservation. In addition, in patients triggered with hCG, freezing all embryos and luteal-phase GnRH antagonist administration should be considered for the outpatient management of severe early OHSS and prevention of late OHSS.STUDY FUNDING/COMPETING INTEREST(S)NHMRC Early Career Fellowship (GNT1147154) to C.A.V. No conflict of interest to declare.TRIAL REGISTRATION NUMBERN/A.

Corticosteroids Prior to Embryo Transfer in Assisted Reproduction in Women with Crohn's Disease and Ulcerative Colitis - A Nationwide Cohort Study.

PurposeFormer studies have suggested that women with Crohn’s disease (CD) and ulcerative colitis (UC) have a decreased chance of a live born child after assisted reproductive technology (ART) treatment. It is debated whether corticosteroids before ART may improve outcomes, either by decreasing inflammatory bowel disease-related inflammation or increasing endometrial receptivity. We examined the efficacy of corticosteroids before embryo transfer in women with CD and UC.Patients and MethodsOur cohort study is based on nationwide Danish health registries, comprising women with CD and UC receiving an embryo transfer (1 January 2006 through 2017). Exposed cohorts constituted women with CD and UC who had received corticosteroids within three months before embryo transfer, and the unexposed cohorts women with CD and UC who did not receive corticosteroids. Our primary outcome was live birth. We controlled for multiple covariates in the analyses.ResultsWe examined 2408 embryo transfers. In patients with CD, 114 embryo transfers were preceded by a corticosteroid prescription, and 964 were not. The corresponding numbers in UC were 122 and 1208, respectively. The adjusted odds ratio (aOR) for live birth in women with CD receiving corticosteroids before embryo transfer, relative to women with CD not receiving corticosteroids, was 0.89 (95% CI 0.49–1.63). The corresponding aOR in UC was 0.98 (95% CI 0.55–1.74).ConclusionCorticosteroids prior to ART in women with CD and UC did not increase the chance of a live born child. The exact impact of corticosteroids prior to embryo transfer in patients with CD and UC still remains to be determined.