Oocyte in-vitro maturation primed with letrozole-HCG versus FSH-HCG in women with oocyte maturation abnormalities: a retrospective study.

RESEARCH QUESTION: Are there differences between in-vitro maturation (IVM) primed with letrozole-human chorionic gonadotrophin (HCG) and IVM primed with FSH-HCG in women with oocyte maturation abnormalities (OMAs), defined as at least two failed IVF cycles where immature oocytes were retrieved? DESIGN: This retrospective study was conducted at a private fertility clinic from January 2009 to April 2023. The final analysis included 75 women in Group 1 (IVM primed with FSH-HCG) and 52 women in Group 2 (IVM primed with letrozole-HCG). RESULTS: A significantly higher median number of oocytes was obtained in Group 1 compared with Group 2 {9 [interquartile range (IQR) 1-5] versus 5 (IQR 1-18); P < 0.001}. However, no differences in oocyte maturation stage at collection were found between the groups (P > 0.05). At the end of IVM, Group 1 had 73/666 mature oocytes and Group 2 had 106/322 mature oocytes, and the median metaphase II oocyte rate per patient was higher in Group 2 [33.3% (IQR 66.7-100.0%) versus 0.0% (IQR 0.0-22.2%); P < 0.001]. Moreover, Group 2 demonstrated a higher median fertilization rate [66.7% (IQR 50.0-100.0%) versus 50.0% (IQR 0.0-66.7%); P = 0.027]. Group 2 had a higher proportion of Grade 2 embryos (58.5% versus 6.3%), and Group 1 had a higher proportion of Grade 3 embryos (93.8% vs 24.4%; P < 0.001). Notably, all pregnancies obtained in the study were in Group 2 (5 versus 0; P = 0.042). CONCLUSIONS: IVM primed with letrozole-HCG in women with prior failed IVF cycles due to OMAs may result in mature oocytes, clinical pregnancies and live births. The effectiveness of letrozole priming for the subtypes of OMAs needs further investigation, with studies including greater numbers of cases.

Comparison of luteal phase and follicular phase in-vitro maturation in women with oocyte maturation abnormalities.

RESEARCH QUESTION: Are there differences in immature oocyte retrieval following luteal phase in-vitro maturation (IVM) compared with follicular phase IVM in women with oocyte maturation abnormalities (OMAs). DESIGN: From January 2019 to May 2023, a retrospective cohort study at a private IVF centre included 36 women with 53 IVM cycles in Group 1 (follicular phase) and 24 women with 32 IVM cycles in Group 2 (luteal phase). Additionally, nine women had both follicular and luteal phase IVM cycles for intracycle variability analysis. RESULTS: There were no differences in oocyte maturation stages between the groups at collection. Group 1 and Group 2 exhibited comparable median metaphase II oocyte rates per patient at 48 h after collection [40.0%, interquartile range (IQR) 0.0-66.7% versus 22.5%, IQR 0.0-52.9%] (P = 0.53). The median fertilization rate in Group 1 (66.7%, IQR 50.0-66.7%) was found to be comparable with that in Group 2 (66.7%, IQR 50.0-66.7%). There were no significant differences in the yielded embryo grades and pregnancy rates between the groups. Comparing follicular and luteal phase IVM within the same menstrual cycle in nine patients, no differences were observed in metaphase II oocyte maturation rates (P > 0.05). CONCLUSIONS: This study found no significant differences in oocyte maturation, fertilization rate, embryo quality or pregnancy outcomes between luteal phase and follicular phase IVM in women with OMAs. These findings suggest that luteal phase IVM can be used similarly to follicular phase IVM, offering a potential avenue to enhance embryo yield for women with OMAs.

A report of two homozygous TERB1 protein-truncating variants in two unrelated women with primary infertility.

PURPOSE: To investigate the genetic etiology of patients with female infertility. METHODS: Whole Exome Sequencing was performed on genomic DNA extracted from the patient's blood. Exome data were filtered for damaging rare biallelic variants in genes with possible roles in reproduction. Sanger sequencing was used to validate the selected variants and segregate them in family members. RESULTS: A novel homozygous likely pathogenic variant, c.626G>A, p.Trp209*, was identified in the TERB1 gene of the patient. Additionally, we report a second homozygous pathogenic TERB1 variant, c.1703C>G, p.Ser568*, in an infertile woman whose azoospermic brother was previously described to be homozygous for her variant. CONCLUSIONS: Here, we report for the first time two homozygous likely pathogenic and pathogenic TERB1 variants, c.626G>A, p.Trp209* and c.1703C>G, p.Ser568*, respectively, in two unrelated women with primary infertility. TERB1 is known to play an essential role in homologous chromosome movement, synapsis, and recombination during the meiotic prophase I and has an established role in male infertility in humans. Our data add TERB1 to the shortlist of Meiosis I genes associated with human infertility in both sexes.

TUBB8 mutations as a cause of oocyte maturation abnormalities: presentation of oocyte and embryo profiles and novel mutations.

RESEARCH QUESTION: What are the embryonic profiles and oocyte maturation dynamics in patients with tubulin beta eight class VIII (TUBB8) mutations leading to oocyte maturation abnormalities (OMAS), and are pregnancies possible in this population? DESIGN: A prospective cohort study was undertaken in a private fertility clinic between January 2019 and December 2022. Whole-exome genomic studies (WES) were performed to detect mutation types. In-vitro maturation (IVM) was compared in 18 subjects: nine with TUBB8 mutations, and nine without TUBB8 mutations to act as the control group. The distributions of oocyte maturation and embryonic development profiles were recorded. IVF and IVM outcomes of the 18 cases were evaluated. The primary outcomes were the embryonic profiles and maturation dynamics of oocytes derived from IVF or IVM in women as related to TUBB8 mutations. RESULTS: Mutations were detected in 52 of 89 (58.4%) women who underwent WES analysis. Twelve TUBB8 mutations were detected in nine women (10.1%) with OMAS. Seven novel TUBB8 mutations were noted. Two pregnancies were obtained in women with c.535 G>A TUBB8 mutations. When comparing IVM outcomes between women with and without TUBB8 mutations, there were no differences in oocyte, embryo or pregnancy parameters (P>0.05 in all cases). CONCLUSIONS: It is clear that further TUBB8 mutations which cause oocyte or embryonic arrest will be detected in future. Although biochemical or ectopic pregnancies may be possible in some of these women, no live births or ongoing pregnancies have been reported to date.

Preliminary cost variance modeling to compare autologous intraovarian platelet-rich plasma vs. standard hormone replacement therapy for menopause management.

BACKGROUND: Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will use HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of HRT risks from extended use has piqued interest in safer options. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. METHODS: HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. RESULTS: Mean ± SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about $576 ± 246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean ± SD cost for OPRP at $8,710 ± 4,911/yr ( P < 0.0001 vs. HRT, by T-test). Upper-bound estimates for annual HRT and OPRP costs were $1,341 and $22,232, respectively. CONCLUSIONS: While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT options that are currently marketed.

Three hour abstinence as a treatment for high sperm DNA fragmentation: a prospective cohort study.

PURPOSE: This study sought to compare sperm DNA fragmentation (SDF) in semen specimens after 3 days and then after 3 h of abstinence in men presenting for initial infertility evaluation. METHODS: A prospective cohort study of 112 men undergoing their first semen analysis as part of an infertility work-up was conducted. All participants presented with 3 days of abstinence for a semen analysis and DNA-fragmentation test. Both tests were repeated on a second sample collected 3 h after the first ejaculation. DNA-fragmentation was evaluated with the halo test by one of two technicians blinded to duration of abstinence. Variables analyzed include ejaculate volume, sperm concentration and motility, smoking status, cannabis use, initial specimen DNA fragmentation, and use of sperm-directed anti-oxidant formulations. RESULTS: Among all subjects, DNA fragmentation improved in the 3-h abstinence specimen (34.6 ± 19.4% vs. 23.7 ± 16.0%, p = 0.0001). Among subjects with high DNA fragmentation (> 35%) on the initial specimen, 55% improved into the normal range. Semen volume and sperm concentration decreased (3.1 ± 3.3 ml vs. 1.9 ± 0.8 ml, p < 0.01 and 41 ± 39 vs. 32 ± 31 (millions/ml), p = 0.01), while progressive motility tended to increase. Fifty-eight subjects demonstrated ≥ 30% improvement in SDF in the second specimen as compared to the first. Factors found to correlate with > 30% improvement in DNA fragmentation in the 3-h abstinence specimen compared to 3 days were younger age and use of anti-oxidants. CONCLUSION: High SDF can often be managed with a second ejaculation 3 h after the first in infertile couples, including in males with abnormal semen analyses per the 2010 WHO guide. Apart from SDF levels, changes in sperm quality were not clinically significant in the second specimen and did not increase rates of ICSI. However, a second ejaculation after 3 h probably may reduce the necessity of costly and/or invasive ART strategies.

Comprehensive analysis of 204 sporadic hydatidiform moles: revisiting risk factors and their correlations with the molar genotypes.

Hydatidiform mole (HM) is an aberrant human pregnancy characterized by excessive trophoblastic proliferation and abnormal embryonic development. HM has two morphological types, complete (CHM) and partial (PHM), and non-recurrent ones have three genotypic types, androgenetic monospermic, androgenetic dispermic, and triploid dispermic. Most available studies on risk factors predisposing to different types of HM and their malignant transformation mainly suffer from the lack of comprehensive genotypic analysis of large cohorts of molar tissues combined with accurate postmolar hCG follow-up. Moreover, 10-20% of patients with one HM have at least one non-molar miscarriage, which is higher than the frequency of two pregnancy losses in the general population (2-5%), suggesting a common genetic susceptibility to HM and miscarriages. However, the underlying causes of the miscarriages in these patients are unknown. Here, we comprehensively analyzed 204 HM, mostly from patients referred to the Quebec Registry of Trophoblastic Diseases and for which postmolar hCG monitoring is available, and 30 of their non-molar miscarriages. We revisited the risk of maternal age and neoplastic transformation across the different HM genotypic categories and investigated the presence of chromosomal abnormalities in their non-molar miscarriages. We confirm that androgenetic CHM is more prone to gestational trophoblastic neoplasia (GTN) than triploid dispermic PHM, and androgenetic dispermic CHM is more prone to high-risk GTN and choriocarcinoma (CC) than androgenetic monospermic CHM. We also confirm the association between increased maternal age and androgenetic CHM and their malignancies. Most importantly, we demonstrate for the first time that patients with an HM and miscarriages are at higher risk for aneuploid miscarriages [83.3%, 95% confidence interval (CI): 0.653-0.944] than women with sporadic (51.5%, 95% CI: 50.3-52.7%, p value = 0.0003828) or recurrent miscarriages (43.8%, 95% CI: 40.7-47.0%, p value = 0.00002). Our data suggest common genetic female germline defects predisposing to HM and aneuploid non-molar miscarriages in some patients.

Correction: Comprehensive analysis of 204 sporadic hydatidiform moles: revisiting risk factors and their correlations with the molar genotypes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

What Are the Patient-reported Outcomes, Complications, and Radiographic Results of Lumbar Fusion for Degenerative Spondylolisthesis in Patients Younger Than 50 Years?

BACKGROUND: The number of young patients with degenerative lumbar spondylosis is expected to increase, and with it, the number of younger patients seeking surgical treatment is likely to rise. The goals of young patients with degenerative spondylolisthesis may differ from those of older patients, but little is known about the levels of pain and function, complication rates, or radiographic union that young patients achieve after interbody fusion. QUESTIONS/PURPOSES: (1) How likely were patients younger than 50 years to achieve a minimal clinically important difference (MCID) in improvement on any of several validated patient-reported outcomes scores after transforaminal lumbar interbody fusion for degenerative spondylolisthesis at a minimum of 2 years after surgery? (2) What proportion developed complications or underwent reoperations? (3) What proportion achieved radiographic fusion or developed adjacent-segment degeneration? METHODS: Longitudinally maintained institutional registry data of patients undergoing primary, single-level, transforaminal lumbar interbody fusion for degenerative spondylolisthesis at a single institution from 2006 to 2013 were studied in this retrospective case series. Of the 96 patients who met inclusion criteria, 14% (13 of 96) were missing follow-up data, leaving 83 patients younger than 50 years with complete clinical and radiological data at a minimum of 2 years (97%, 93 of 96 had sufficient data to assess complications and radiographic fusion). The mean age of the cohort was 44 ± 7 years. Radiological parameters for each patient with spondylolisthesis were recorded. Clinical outcomes such as the numeric rating scale for back pain and leg pain, Oswestry Disability Index (ODI) and SF-36 were assessed preoperatively and postoperatively at 1, 3, 6 months and 2 years. The proportion of patients who had an improvement greater than the MCID of each outcome instrument was then calculated. The occurrence of any medical, surgical or wound complications, and reoperations for any reason were recorded. Radiographic fusion using Bridwell grading and adjacent-segment degeneration were assessed by an independent observer not involved in clinical care. The mean follow-up was 5 ± 3 years. RESULTS: The proportions of patients younger than 50 years who achieved the MCID for the various patient-reported outcomes were 82% (68 of 83) for leg pain, 75% (62 of 83) for back pain, 87% (72 of 83) for ODI and 71% (59 of 83) for SF-36 physical component summary at 2 years. Two perioperative complications occurred, and two reoperations were performed for implant-related complications. A total of 85% (79 of 93) of young patients achieved stable fusion, 8% (seven of 93) had radiologic adjacent-segment degeneration, and one patient underwent a revision procedure. CONCLUSIONS: Young patients with lumbar degenerative spondylolisthesis commonly, but do not always, experience clinically meaningful gains in pain relief, function, and quality of life after transforaminal lumbar interbody fusion. A low risk of complications, reoperations, nonunion and adjacent-segment degeneration were also noted in this population. LEVEL OF EVIDENCE: Level III, therapeutic study.

Elderly Patients Undergoing Minimally Invasive Transforaminal Lumbar Interbody Fusion May Have Similar Clinical Outcomes, Perioperative Complications, and Fusion Rates As Their Younger Counterparts.

BACKGROUND: Although several studies have suggested that minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) may be especially beneficial in the elderly population due to lower operative morbidity and faster postoperative recovery, there are limited studies investigating the functional outcomes, quality of life, and satisfaction in elderly patients after MIS-TLIF. Furthermore, existing studies had substantial clinical, diagnostic, and surgical heterogeneity. QUESTIONS/PURPOSES: We asked if elderly patients could experience comparable (1) patient-reported pain, disability and quality of life, (2) perioperative complications, and (3) radiological fusion rates as their younger counterparts after MIS-TLIF. METHODS: Prospectively collected registry data of patients undergoing primary, single-level, MIS-TLIF for degenerative spondylolisthesis between 2012 and 2014 were reviewed. We included 168 patients, 39 of whom were at least 70 years old. Of the 129 patients younger than 70 years old, propensity-score matching was used to select 39 younger controls with adjustment for sex, BMI, American Society of Anesthesiologists score, and baseline clinical outcomes. Perioperative complications and radiologic data were compared. RESULTS: There was no difference in back pain (mean difference -0.3 [95% confidence interval -1.0 to 0.5]; p = 0.52); leg pain (mean difference -0.1 [95% CI to 0.6-0.5]; p = 0.85); Oswestry Disability Index (mean difference -2.9 [95% CI -8.0 to 2.2]; p = 0.26); and SF-36 physical (mean difference 3.0 [95% CI -0.7 to 6.8]; p = 0.107); and mental component summary (mean difference 1.9 [95% CI -4.5 to 8.2]; p = 0.56); up to 2 years postoperatively; 85% of younger patients and 85% of elderly patients were satisfied (p > 0.99) while 87% and 80%, respectively, had fulfilled expectations (p = 0.36). Four perioperative adverse events occurred in each group. There was also no difference in the rate of fusion (87% in younger patients and 90% in elderly patients; p = 0.135). CONCLUSIONS: When clinical and surgical heterogeneity were minimized, elderly patients undergoing minimally invasive transforaminal lumbar interbody fusion not only had comparable rates of perioperative complications but also experienced similar improvements in pain, function, and quality of life. A high rate of satisfaction was achieved. LEVEL OF EVIDENCE: Level II, prognostic study.

A comparison of two months pretreatment with GnRH agonists with or without an aromatase inhibitor in women with ultrasound-diagnosed ovarian endometriomas undergoing IVF.

RESEARCH QUESTION: Does the addition of an aromatase inhibitor improve IVF outcomes in women with endometriomas when pretreating them with gonadotrophin-releasing hormone agonists? DESIGN: Retrospective two-centre cohort study involving 126 women aged 21-39 years who failed a previous IVF cycle and all subsequent embryo transfers and had sonographic evidence of endometriomas. Women were non-randomly assigned to either 3.75 mg intramuscular depo-leuprolide treatment alone or in combination with 5 mg of oral letrozole daily for 60 days prior to undergoing a fresh IVF cycle. Main outcome measures included clinical pregnancy rate and ongoing pregnancy rate after 24 weeks' gestation. RESULTS: Prior to treatment, antral follicle count (AFC), basal serum FSH and endometrioma diameter did not differ between groups. After treatment, AFC differed between letrozole and non-letrozole-treated groups (10.3 ± 2.0 versus 6.4 ± 2.5; P = 0.0001), as did mean endometrioma maximum diameter (1.8 ± 0.4 cm versus 3.2 ± 0.8 cm; P = 0.0001). At IVF, the gonadotrophin dose used was significantly lower in letrozole-treated subjects (2079 ± 1119 versus 3716 ± 1314; P = 0.0001), the number of mature oocytes collected was greater (9.1 ± 2.4 versus 4.0 ± 1.7; P = 0.0001), as were the number of two-pronuclear embryos and number of blastocysts. The clinical pregnancy rate was significantly higher in the letrozole-treated group (50% versus 22%, P = 0.003), as was the live birth rate (40% versus 17%, P = 0.008). CONCLUSIONS: The combination of depo-leuprolide acetate monthly for 60 days combined with daily letrozole has better clinical outcomes at IVF in women with endometriomas than depo-leuprolide acetate treatment alone.

Vaginal ultrasound-guided ovarian needle puncture compared to laparoscopic ovarian drilling in women with polycystic ovary syndrome.

STUDY OBJECTIVE: To compare pregnancy outcomes in PCOS women undergoing transvaginal ovarian injury (TVOI) and laparoscopic ovarian drilling (LOD) DESIGN: 126 infertile patients with PCOS were included in this prospective cohort study CANADIAN TASK FORCE CLASSIFICATION OF LEVEL OF EVIDENCE: IIA. SETTING: University-affiliated fertility center. PATIENTS: Sixty-seven infertile patients with the history of failed in vitro maturation underwent follow-up as the TVOI group. Fifty-nine infertile women who underwent LOD acted as controls. All subjects had PCOS with menstrual irregularity and were anovulatory by repetitive serum progesterone levels. INTERVENTIONS: The LOD group underwent six cauterizations of a single ovary with 30W for 4-6 s. Failed IVM subjects with 20-30 needle punctures per ovary acted as the TVOI group. Subjects were followed for six months. MEASUREMENTS AND MAIN RESULTS: There was not a significant difference between the groups when the cases were evaluated in terms of spontaneous pregnancy or miscarriage rates. BMI levels decreased in both the TVOI and the LOD groups in a similar fashion. However, serum AMH and AFC decreased greater after LOD than they did with TVOI over the six-month duration of the study (p < 0.001 in both cases). CONCLUSIONS: Preliminary data suggest that TVOI likely represents a safer, less costly and equally effective manner of surgical ovulation induction in anovulatory PCOS women when compared to LOD.

Combined modalities for the prevention of ovarian hyperstimulation syndrome following an excessive response to stimulation.

Although the classification and management of ovarian hyperstimulation syndrome (OHSS) are well described in the literature, little attention has been given to modalities that aim to prevent its occurrence. In this retrospective study, we sought to investigate whether a combination of modalities in addition to GnRH agonist triggering in GnRH antagonist cycles could result in better prevention of OHSS. The study included 170 hyperresponder patients who were stimulated with GnRH antagonist protocol and were triggered with GnRH agonist for final oocyte maturation. Freeze all embryos was performed in all patients. The intervention group included treatment with dopamine agonist and restarting the GnRH antagonist. Of the 170 patients included, 63 were included in the intervention group. Compared to no intervention, women in the intervention group were more likely to have: menses within 7 days of the oocyte retrieval, smaller ovarian diameter, the absence of free pelvic fluid, less hemoconcentration and higher serum sodium levels. It can be concluded that combining other modalities in addition to triggering with GnRH agonist in GnRH antagonist cycles, results in targeting several pathways that lead to OHSS and result in rapid resolution of signs of ovarian hyperstimulation.

Predictive factors for live birth after in vitro maturation of oocytes in women with polycystic ovary syndrome.

OBJECTIVE: In vitro maturation (IVM) of human oocytes can be an alternative treatment option to conventional in vitro fertilization. Women with polycystic ovary syndrome (PCOS) are considered the classical candidates for IVM because of the associated ovarian morphology and because IVM diminishes the risk of developing ovarian hyperstimulation syndrome. The objective of this study was to identify predictive factors for live birth in a cohort of women with PCOS who underwent IVM. METHODS: This retrospective study included 159 patients with PCOS who had IVM cycles in which single or double embryo transfer was performed. The IVM protocol included three days of gonadotropin ovarian stimulation and hCG priming when the leading follicle size was 10-12 mm. Collected cumulus-oocyte complexes were cultured for 24 h for maturation. Intracytoplasmic sperm injection (ICSI) was used for fertilization. Embryo transfer was performed two days after fertilization. Demographic and clinical parameters were analyzed with logistic regression to identify predictors for live birth. RESULTS: The women's mean age was 27.4 years, the mean number of retrieved oocytes was 14, and the live birth rate was 34.6%. The logistic regression revealed the following significant factors for live birth: infertility duration (OR 0.9; 95% CI, 0.82-0.98), number of collected oocytes (OR 1.56; 95% CI, 1.01-3.2), embryo cell number (OR 2.1; 95% CI, 1.4-3.5), and embryo grade (OR 1.84; 95% CI, 1.13-4.2). CONCLUSION: Infertility duration, oocyte number, embryo cell number, and embryo grade were the most significant predictors for live birth after IVM in PCOS patients. These prognostic factors can be used when planning treatment or counselling patients.

Beneficial effects of glutathione supplementation during vitrification of mouse oocytes at the germinal vesicle stage on their preimplantation development following maturation and fertilization in vitro.

Oocyte cryopreservation is imperative for assisted reproductive technologies (ART). Although cryopreservation of oocytes at the Metaphase II has been widely used, immature oocytes at the germinal vesicle stage (GV-oocytes) need to be cryopreserved in certain situations such as cancer patients; however, the success rate of embryonic development from the GV-oocytes remains low largely due to the requirement for in vitro maturation (IVM). Our aim was to investigate the effects of glutathione (GSH) supplementation during vitrification and warming of mouse GV-oocytes on the preservation of developmental competence. GV-oocytes within cumulus oocyte complexes (COCs) were collected from C57BL/6J (B6) and (B6.DBA)F1 mouse strains and subjected to vitrification and warming, followed by IVM. The vitrification, warming or IVM medium was supplemented with GSH at 0-4.0 mM. In vitro matured oocytes were then fertilized in vitro and cultured in KSOMaa up to 4 days. The first cleavage and blastocyst development were evaluated morphologically, and their rates were statistically analysed by one-way ANOVA followed by Tukey's multiple comparisons test. The difference was considered significant at P < 0.05. The results showed that GSH supplementation in the IVM medium exhibited no or rather inhibitory effects on the first cleavage or blastocyst development in both mouse strains except that 1.0 mM GSH increased the blastocyst development rate in B6. By contrast, 1 mM GSH supplementation during vitrification and warming increased the blastocyst development rate in both mouse strains, more efficiently in B6 than (B6.DBA)F1. In conclusion, GSH supplementation during vitrification and warming of GV-oocytes protects the oocytes from freezing-inflicted loss of developmental competence.

Comorbidities Have a Greater Impact Than Age Alone in the Outcomes of Octogenarian Total Knee Arthroplasty.

BACKGROUND: Increasing age and various comorbidities are known risk factors for complications after total knee arthroplasty (TKA), but data on the impact of total comorbidity burden is scarce. We investigated the effect of age and total comorbidity burden on outcomes after primary TKA in octogenarians (OGs). METHODS: A matched-pair comparison study was conducted using prospectively collected TKA registry data in a large tertiary institution. Between 2006 and 2011, consecutive OGs undergoing primary unilateral TKA, with minimum 2-year follow-up, were matched 1:1 with younger controls based on demographic and surgical variables. We compared the Charlson comorbidity index (CCI), complication rate, length of stay (LOS), 30-day readmission, and 2-year reoperation rate. Multivariate analysis was performed to determine the effects of age and CCI on each outcome. RESULTS: There were 209 OGs and 209 controls. OGs were significantly older (mean age 82.1 vs 66.1 years, P < .001) and had higher CCI. OGs had longer mean LOS (6.3 vs 5.4 days, P = .001), and a trend for more complications and readmissions. The complication rate increased from 7.5% for CCI = 0, to 33.3% for CCI ≥3 (P = .005). The LOS increased from 5.4 days for CCI = 0, to 9.6 days for CCI ≥3 (P < .001). Multivariate analysis showed that higher CCI was an independent risk factor for complications and longer LOS, whereas age was not. CONCLUSION: Comorbidity burden has a greater impact than age alone on TKA outcomes in OGs. Well-selected OGs remain good candidates for TKA.

Clinical definition paper on in vitro maturation of human oocytes.

In vitro maturation (IVM) of human oocytes is a reproductive technique which has been practiced for 25 years and is gaining popularity. However, the techniques used for IVM differ substantially across clinics and they result in extremely variable pregnancy rates, partially due to some of these differences in protocols. Such differences include the use in some cycles of hCG triggering prior to oocyte retrieval and the use of a few days of gonadotrophin treatment to support moderate follicle growth. Other important factors are patient selection (including those with polycystic ovaries or decreased ovarian reserve), the number of embryos transferred and cleavage-stage embryo or blastocyst transfer. There are also substantial differences of opinion among clinicians regarding IVM and what it implies. Due to the large variation in protocols, a decision was made to write this paper in an attempt to introduce uniformity when comparing treatments and outcomes of IVM. A clinical definition of IVM was developed: The retrieval of oocytes from small and intermediate sized follicles in an ovary before the largest follicle has surpassed 13 mm in mean diameter. The use of short gonadotrophin stimulation should be acknowledged. However, it should be stated that metaphase II oocytes also have the potential to be collected at that time in the cycles associated with either hCG or GnRH agonist priming. Many feel this is not IVM because some mature oocytes are retrieved, therefore, we recommend renaming this procedure either natural cycle IVF or modified natural cycle IVF (if gonadotrophin stimulation is given) with early triggering, combined with IVM The percentage as well as the absolute number of mature oocytes at retrieval should be indicated. The use of these titles will allow transparency when comparing results of IVM cycles.

Early Short Stimulation Modified Natural Cycle IVF With GnRH Agonist Trigger and In Vitro Maturation in a Woman with Polycystic Ovary Syndrome: A Case Report.

BACKGROUND: Gonadotropin-releasing hormone agonist (GnRHa) triggering of final oocyte maturation has been used successfully in GnRH antagonist IVF cycles. It has not been used to date in cycles in which immature oocytes are matured in vitro. CASE: We report here for the first time that GnRHa triggering in a variation on the modified natural IVF cycle can be used as a strategy in the treatment of infertility secondary to polycystic ovary syndrome. In this approach, follicles were stimulated with gonadotropins for three to five days when they were small, and triggering of ovulation occurred when the largest follicles were 10 to 12 mm in diameter. This was followed by retrieval of many immature oocytes that were matured in vitro and subsequently developed to form blastocysts that resulted in a live birth. CONCLUSION: This is the first human evidence that GnRHa triggering of ovulation can be used successfully when the aim is in vitro maturation of oocytes.

Bi-directional communication with the cumulus cells is involved in the deficiency of XY oocytes in the components essential for proper second meiotic spindle assembly.

The oocyte becomes competent for embryonic development by involving mutual communication with cumulus cells (CCs) during folliculogenesis. How this communication takes place under physiological conditions is not fully understood. Current study examined oocyte-CCs communication in the XY sex-revered female mouse. We have previously found that the XY oocyte is defective in its cytoplasm, causing abnormal MII-spindle assembly and a failure in embryonic development. Our present study showed that transcript levels of Pfkp, Pkm2 and Ldh1 involved in glycolysis were lower in the CCs surrounding XY oocytes than in those surrounding XX oocytes. ATP contents in XY oocytes were also lower than those in XX oocytes, suggesting that lower glycolytic gene expression in CCs resulted in lower ATP contents in the enclosed oocyte. Co-culture of oocytectomized CC-oocyte complexes (COCs) with denuded oocytes showed that XY oocytes were less efficient than XX oocytes in promoting glycolytic gene expression in CCs. Furthermore, both glycolytic gene expression levels in CCs and ATP contents in oocytes of XY COCs increased to similar levels to those of XX COCs after culture for 20h in the presence of milrinone (=preincubation), which prevented spontaneous oocyte maturation. By increasing ATP levels in XY oocytes by either COC preincubation or ATP microinjection into oocytes prior to in vitro maturation, an improvement in MII-spindle assembly was observed. We conclude that the XY oocyte produces lesser amounts of paracrine factors that affect its companion CCs, which in turn make the ooplasm deficient in its components, including ATP, essential for MII-spindle assembly.

Do the causes of infertility play a direct role in the aetiology of preterm birth?

BACKGROUND: It is well established that singletons born of assisted reproductive technology are at higher risk of preterm birth and other adverse outcomes. What remains unclear is whether the increased risk is attributable to the effects of the treatment alone or whether the underlying causes of infertility also play a role. The aim of this study was to examine whether any of the six categories of causes of infertility were associated with a direct effect on preterm birth using causal mediation analysis. METHODS: We assembled a hospital-based cohort of births delivered at a large tertiary care hospital in Montreal, Canada between 2001 and 2007. Causes of infertility were ascertained through a clinical database and medical chart abstraction. We employed marginal structural models (MSM) to estimate the controlled direct effect of each cause of infertility on preterm birth compared with couples without the cause under examination. RESULTS: The final study cohort comprised 18,598 singleton and twin pregnancies, including 1689 in couples with ascertained infertility. MSM results suggested no significant direct effect for any of the six categories of causes. However, power was limited in smaller subgroup analyses, and a possible direct effect for uterine abnormalities (e.g. fibroids and malformations) could not be ruled out. CONCLUSION: In this cohort, most of the increased risk of preterm birth appeared to be explained by maternal characteristics (such as age, body mass index, and education) and by assisted reproduction. If these findings are corroborated, physicians should consider these risks when counselling patients.