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Background. While growth hormone (GH) is commonly used as an adjuvant treatment to controlled ovarian stimulation (COS) for in vitro fertilization (IVF) cycles, the data regarding its efficacy is inconsistent. Design. A retrospective matched cohort study of poor responder patients who underwent COS without the use of GH (COS-GH) subsequently followed by COS cycles that included adjuvant GH (COS+GH) treatment. Materials and Methods. A list of all patients having filled a prescription for GH from January 2018 – March 2020 was obtained. GH was administered daily at 3mg (9IU) starting on the first day of stimulation and ending on the day of trigger. Only women who had documentation of a previous cycle without the use of GH were included in the study. Results. 182 cycles (91 patients) were included in the study, and COS-GH cycles were compared to COS+GH cycles. The total dose of gonadotropins used (5757 vs 4252 mIU, p=0.002), duration of stimulation (10.4 vs 10.1 days, p=-.045), maximum Estradiol (E2) (2411 vs 1932 pg/ml, p=0.010), endometrial thickness (11.2 vs 10.6 mm, p=0.010), number of oocytes retrieved (14.2 vs 11.8, p=0.001), number of mature oocytes (11.1 vs 9.7, p=0.028), number of blastocysts (3.98 vs 2.56, p=Conclusions. Adding GH to the COS protocol in poor responder patients may lead to improvements in the number of oocytes retrieved, number of mature oocytes, endometrial thickness, number of blastocysts, the number of usable blastocysts.

Objective To evaluate the diagnostic performance of the antimullerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma. Design Prospective cohort study. Setting Fifteen private and academic fertility centers (14 in the United States and 1 in Canada). Patient(s) Women aged 21–45 years planning controlled ovarian stimulation for in vitro fertilization. Intervention(s) None. Main Outcome Measure(s) Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count. Result(s) Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7–88.5) and a specificity of 59.9% (95% CI 54.2–65.4). Conclusion(s) This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible.

ObjectiveTo use metabolism of cumulus cells (CCs) to predict oocyte competency.DesignCC clumps that associate with oocytes are thought to provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function. This was a prospective and blinded cohort study that analyzed 403 individual sets of CC clumps from 36 participants. Thirty-one of the participants had paired oocyte maturity data. CCs were removed from oocytes after oocyte retrieval procedure, transported individually in vials to the research laboratory, incubated with stable isotope labeled substrates for 60 minutes, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA derived from the stable isotope labeled substrates.ResultsMean enrichment of M+2 acetyl-CoA (mean, standard deviation), where M+0 is the unlabeled acetyl-CoA, M+1 contains 1 13C, M+2 contains 2 13C atoms, was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Mean % enrichment of acetyl-CoA from acetate in CCs from women ≤34 (49.06, 12.73) decreased with age compared to CCs from women >34 (43.48, 16.20) (p=0.0004, t test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M+2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: −6.02, CI: −1.74,−13.79, p=0.013). Limitations of this preliminary study include the difficulty in recovery of consistent numbers of CCs across oocytes, and the inability in this study to track oocyte function to the primary endpoint of successful birth.ConclusionAcetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of short chain fatty acids like acetate should be investigated relative to oocyte function and age-related fertility.

PURPOSE: Oocyte competence is critical in success of assisted reproduction. Metabolic signaling between oocyte and cumulus cells within the cumulus-oocyte complex procure oocyte development. This study evaluated the relationship between respirometric activity of cumulus cells and maturity of corresponding oocytes. METHODS: In prospective cohort study, 20 women of age 28–42 undergoing IVF procedure were involved. To evaluate oocyte maturity, the cumulus cells from individual oocytes were assessed flow cytometrically by double labeling of cells with mitochondria specific dyes. The respirometric stress analysis using ATPase inhibitor oligomycin was applied to assess mitochondria metabolic abnormalities. RESULTS: The cumulus cells from each of 327 oocytes were analyzed. The respirometric index of cumulus cells (O′(R)) strongly correlates with maternal ovarian reserve, showing to be higher in patients with higher AMH (p

Objective To evaluate a new fully automated antimullerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved. Design Prospective cohort study. Setting Thirteen private and academic fertility centers in the United States. Patients(s) A total of 178 women undergoing their first in vitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC). Intervention(s) None. Main Outcome Measure(s) Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15. Result(s) The mean AMH among the poor responders was 0.74 ng/mL, compared with 3.20 ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93 ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P 15 was 1.75, with specificity of 59.1%. Conclusion(s) A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes.

Herlyn-Werner-Wunderlich syndrome is characterized by a triad of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis. The syndrome should be suspected in any young woman with abdominal pain or cyclic dysmenorrhea, and radiologic evidence of müllerian duct and renal anomalies. Herein is presented the case of a 25-year-old woman with a rare variant of Herlyn-Werner-Wunderlich syndrome, characterized by an anomalous connection between the 2 endocervical canals, who underwent hemivaginal septum resection to relieve progressively worsening dysmenorrhea. The right hemivaginal septum was resected medially from the left cervix and laterally off the right vaginal wall. Hydrodissection between the hemivaginal septum and right cervix facilitated surgical resection. After resection of the hemivaginal septum there was complete resolution of dysmenorrhea and no recurrence of hematometra or hematocolpos.

BACKGROUND: The majority of human embryos created using in vitro fertilisation (IVF) techniques are aneuploid. Comprehensive chromosome screening methods, applicable to single cells biopsied from preimplantation embryos, allow reliable identification and transfer of euploid embryos. Recently, randomised trials using such methods have indicated that aneuploidy screening improves IVF success rates. However, the high cost of testing has restricted the availability of this potentially beneficial strategy. This study aimed to harness next-generation sequencing (NGS) technology, with the intention of lowering the costs of preimplantation aneuploidy screening. METHODS: Embryo biopsy, whole genome amplification and semiconductor sequencing. RESULTS: A rapid (

Objective To determine any beneficial effects of preimplantation genetic screening (PGS) of all chromosomes by array comparative genomic hybridization (aCGH), with either day 3 or blastocyst biopsy, for idiopathic recurrent pregnancy loss (RPL) patients compared with their expected loss rate. Design Case series report. Setting Multiple fertility centers. Patient(s) A total of 287 cycles of couples with idiopathic RPL (defined as two or more losses). Intervention(s) PGS was done with day 3 biopsy (n = 193) or blastocyst biopsy (n = 94), followed by analysis with aCGH. Main Outcome Measure(s) Spontaneous abortion rate, euploidy rate. Result(s) A total of 2,282 embryos were analyzed, of which 35% were euploid and 60% were aneuploid. There were 181 embryo transfer cycles, of which 100 (55%) became pregnant with an implantation rate of 45% (136 sacs/299 replaced embryos) and 94 pregnancies (92%) were ongoing (past second trimester) or delivered. The miscarriage rate was found to be only 6.9% (7/102), compared with the expected rate of 33.5% in an RPL control population and 23.7% in an infertile control population. Conclusion(s) Current PGS results with aCGH indicate a significant decrease in the miscarriage rate of idiopathic RPL patients and high pregnancy rates. Furthermore, this suggests that idiopathic recurrent miscarriage is mostly caused by chromosomal abnormalities in embryos.

to determine if embryo banking with PGS is more optimal than proceeding with PGS regardless of embryo number.patients were divided into 2 groups, group 1 were those that banked embryos and proceeded through another round of IVF prior to PGS, and group 2 underwent PGS regardless of embryo number. Group 2 was divided into group 2A (patients with10 embryos) and group 2B (patients who had10 embryos).there was no difference in embryos biopsied, normal embryos, number transferred, and pregnancy rate between group 1 and 2. A significant number of patients did not have a transfer in group 2B (6/11) compared to group 1 (3/19) (P = 0.0419). There was no significance between pregnancy rates per transfer between group 1 (6/16) and group 2B (2/5).our data suggests that banking will increase the odds of going to transfer but there was no increase in pregnancy rates.

A laser is commonly used to remove a blastomere from an embryo for genetic testing. The laser uses intense heat which could possibly disrupt embryo development. It is the goal of this study to test the effects of different laser pulse lengths (and consequently heat) on the embryo biopsy procedure and embryo development. Each embryo biopsy was performed randomly utilizing laser pulse lengths of 0.604mS (group I), 0.708mS (group II), and 1.010mS (group III). For groups I, II, and III, 83, 86, and 71 embryos were biopsied, respectively. There was no difference in day 5 embryo quality or lysed blastomeres between groups. Average number of blastomeres biopsied between group I (1.0 ± 0.0), II (1.0 ± 0.2), and III (1.1 ± 0.2) was significant (0.0001). Our data demonstrates that laser pulse length does not influence the embryo biopsy procedure or embryo development.

This study retrospectively analysed array comparative genomic hybridization (CGH) results of 7753 embryos from 990 patients to determine the frequency of embryonic euploidy and its relationship with the cohort size (i.e. the number of embryos available for biopsy and array CGH analysis). Linear regression analysis was performed to assess the effect of cohort size on euploidy rate adjusted for the effect of female age. While increasing female age was associated with a significant decrease in euploidy rate of day-3 and day-5 embryos (P < 0.001 for both groups), cohort size was not significantly associated with euploidy rate. Logistic regres- sion analysis was performed to assess the effect of cohort size, adjusted for maternal age, on the likelihood of having at least one euploid embryo available for transfer. The odds of having at least one euploid embryo in an assisted cycle was significantly decreased by increasing female age (P < 0.01 for both day-3 and day-5 embryos) and was significantly increased by every additional embryo available for analysis (P < 0.001 for both day-3 and day-5 embryos). RBMOnline

Objective To report a clinical pregnancy after rebiopsy and vitrification of blastocysts following allele dropout (ADO) of biopsied day 3 embryos. Design Case report. Setting Private center. Patient(s) Thirty-year-old woman and her 33-year-old husband who carries the single-gene condition paraganglioma. Intervention(s) In vitro fertilization with day 3 embryo biopsy–ET–blastocyst biopsy and vitrification–subsequent frozen ET cycle. Main Outcome Measure(s) Results from preimplantation genetic diagnosis and pregnancy results after fresh and frozen ETs. Result(s) Nineteen oocytes were retrieved of which 13 were mature and 12 fertilized. Eleven embryos were biopsied on day 3: two were normal, five were affected, and four exhibited ADO. The two normal blastocysts were transferred, and three of the ADO blastocysts were biopsied and sent for reanalysis. The biopsied blastocysts were vitrified. No pregnancy resulted from the fresh ET. One of the biopsied blastocysts was normal, one received no result, and one exhibited ADO. A singleton clinical pregnancy resulted from a subsequent frozen ET of the thawed biopsied normal blastocyst. Conclusion(s) Rebiopsy and vitrification of blastocysts could be used in cases of ADO or lack of results after day 3 embryo biopsy.

OBJECTIVE: To determine if vitrification (Vit) can provide improved survival and pregnancy rates compared to a modified slow freeze protocol that had proven very successful for 2PN and multi-cell embryos over the years. DESIGN: Prospective comparison with Vit. performed 3 set days each week vs. 4 for slow freeze. MATERIALS AND METHODS: Vit. protocol: Irvine media, 6-10 minutes in equilibration solution and 90 seconds in vitrification solution at room temperature then loaded onto High security vitrification (HSV) highsecurity straw in

blastocyst biopsy. The practice of biopsying all non-arrested D5 embryos provides the opportunity to have genetic information on all embryos eligible for fresh transfer on D6, potentially adding to the pool of embryos available for transfer. Biopsy of non-arrested D5 embryos may also avoid the need to cryopreserve developmentally competent embryos without ploidy information at the time of transfer.

Purpose A laser is commonly used to remove a blastomere from an embryo for genetic testing. The laser uses intense heat which could possibly disrupt embryo development. It is the goal of this study to test the effects of different laser pulse lengths (and consequently heat) on the embryo biopsy procedure and embryo development. Methods Each embryo biopsy was performed randomly utilizing laser pulse lengths of 0.604mS (group I), 0.708mS (group II), and 1.010mS (group III). Results For groups I, II, and III, 83, 86, and 71 embryos were biopsied, respectively. There was no difference in day 5 embryoqualityorlysedblastomeresbetweengroups.Average number of blastomeres biopsied between group I (1.0±0.0), II (1.0±0.2), and III (1.1±0.2) was significant (0.0001). Conclusion Our data demonstrates that laser pulse length does not influence the embryo biopsy procedure or embryo development.