A prospective proof-of-concept trial on the effect of personalized dosages of follitropin delta in intrauterine insemination.

RESEARCH QUESTION: What is the efficacy and safety of individualized follitropin delta dosing for ovarian stimulation in intrauterine insemination (IUI)? DESIGN: This single-centre, prospective, open-label, single-cohort study involving 106 patients established an original dosing regimen based on body weight and anti-Müllerian hormone (AMH) concentrations, with adjustments based on the ovarian response from the previous IUI cycle. Each participant was enrolled in a maximum of three IUI cycles. RESULTS: Mean age was 34.5 ± 4.5 years, mean weight 69.2 ± 11.2 kg, mean AMH 15.7 ± 8.6 pmol/l, mean FSH 6.3 ± 2.6 IU/l and mean antral follicle count 16.4 ± 8.2. The percentage of patients who produced more than three mature follicles was 1.9%, 0% and 1.5%, respectively, for the three IUI cycles. The percentage of patients with two or three mature follicles was 34.0%, 36.9% and 47.1% for the three IUI cycles. The clinical pregnancy rate per IUI cycle was 17.9%, 14.3% and 17.6% for the three cycles, with a cumulative clinical pregnancy rate of 40.6%. Out of 258 cycles, 43 (16.7%) resulted in clinical pregnancy, with six of those resulting in multiple pregnancies (14.0%). Two resulted in spontaneous reduction within the first trimester and four resulted in live twin births, representing only 1.6% of the total cycles. CONCLUSIONS: This study is the first to utilize follitropin delta for stimulation in IUI. It demonstrates that individualized dosing is both effective and safe, resulting in satisfactory cumulative pregnancy rates and an acceptable multiple pregnancy rate, thus achieving the primary objectives of the research.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3-4 and [Formula: see text] 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78-7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with [Formula: see text] 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

In freeze-all embryo cycles due to endometrial fluid (EF), live birth rates are comparable to those of controls, despite high rates of EF recurrence and cycle cancellation.

RESEARCH QUESTION: Do cumulative live birth rates (CLBRs) differ between women who have had a freeze-all embryo cycle (FAE) for endometrial fluid (EF) and controls? DESIGN: This retrospective cohort study included 83 women who had a FAE cycle due to the presence of EF between 2010 and 2016 at a university-affiliated private IVF center. The controls were 219 women who had FAE for other indications during the same period and were randomly selected. The main outcome measures were CLBRs, EF recurrence, cancellation and pregnancy loss rates. RESULTS: Population characteristics were comparable between the two groups. The CLBR was not significantly different between the EF and the control group: 39.8 % vs. 47.0 %, respectively, p=0.26. Cancellation rates in the two first FETs were higher in the EF group than the control group: 18.1 % vs. 4.1 % (p<0.001) and 22.9 % vs. 8.5 % (p=0.02). After FAE for EF, we observed a significant risk of EF recurrence (32/177 cycles, 18.1 %), allowing us to identify a poor prognosis subgroup. When EF was detected, the LBR per transfer was 7.1 % (1/14) when the transfer was finally performed (after EF aspiration or EF disappearance), compared to 25 % (32/128) in cycles without EF recurrence (p<0.05). Conversely, in the absence of EF recurrence (145/177, 81.9 %), the LBR was comparable to that of the control group. The type of endometrial preparation does not seem to be associated with EF recurrence. CONCLUSION: Despite higher rates of EF recurrence and cycle cancellation, women with FAE for EF ultimately have comparable LBRs to those who have had a FAE for other indications. However, women presenting with at least one EF recurrence during FETs seem to have a lower LBR.

Individualized ovarian stimulation for in vitro fertilization: a multicenter, open label, exploratory study with a mixed protocol of follitropin delta and highly purified human menopausal gonadotropin.

OBJECTIVE: To evaluate the safety profile and the number of usable blastocysts on day 5 and on day 6 after treatment with an individualized dosing regimen of a follitropin delta and highly purified human menopausal gonadotropin (HP-hMG) for controlled ovarian stimulation. DESIGN: Multicenter, open label, exploratory study. SETTING: Reproductive medicine clinics. PATIENT(S): A total of 110 patients (aged 18-40 years). INTERVENTION(S): Follitropin delta coadministered with HP-hMG, with follitropin delta dose fixed according to an established algorithm and HP-hMG dose at 75 IU when the follitropin delta starting dosage was <12 µg; 150 IU when follitropin delta dosage was 12 µg and weight <100 kg, and 225 IU when follitropin delta dosage was 12 µg and weight ≥100 kg (dosage adjustments confined to HP-hMG only). MAIN OUTCOME MEASURE(S): Mean number of good-quality blastocysts obtained at day 5 and day 6 as well as the proportion of women with ovarian hyperstimulation syndrome (OHSS). RESULT(S): A cohort study was compared with the follitropin delta group from the Evidence-based Stimulation Trial with Human Recombinant Follicle-Stimulating Hormone in Europe and Rest of World 1 (ESTHER-1) study. Even when stratified by age, a statistically significantly higher mean in the number of oocytes retrieved and number of good-quality blastocysts was observed in this study compared with the ESTHER-1 trial in which follitropin delta was used alone. The rate of patients triggered with a gonadotropin-releasing hormone agonist was statistically significantly higher in our Menopur and Rekovelle Combined Study (MARCS) cohort (43%) when compared with the rates reported in the follitropin delta cohort in the ESTHER-1 study (2.3%). Incidence of any grade of OHSS was 9.3% in the present study compared to 2.6% in follitropin delta group from ESTHER-1 trial. No cases of moderate or severe OHSS were observed in our study compared with 1.4% in the follitropin delta group of ESTHER-1. CONCLUSION(S): Optimizing the ovarian response during in vitro fertilization employing a mixed protocol of individualized dosing of follitropin delta and HP-hMG resulted in a statistically significant number of usable blastocysts on days 5 and 6 with an increased risk of mild OHSS, which did not require medical intervention or hospitalization. CLINICAL TRIAL REGISTRATION NUMBER: NCT03483545.

Obesity and Infertility: A Metabolic Assessment Strategy to Improve Pregnancy Rate.

BACKGROUND: The metabolic global approach is a multidisciplinary intervention for obese women before undergoing assisted reproductive techniques, with the goal of improving fertility and decreasing adverse pregnancy outcomes. The objective of this study was to evaluate the impact of the metabolic global approach on pregnancy rate. METHODS: This retrospective cohort study included 127 women and was conducted at the Centre hospitalier de l'Université de Montréal fertility center. Eligibility included BMI at initial consultation of ≥30 kg/m 2. Fertility treatments were considered when a weight loss of minimum 5% and normal metabolic indices were achieved. The p<0.05 was considered statistically significant. RESULTS: Median baseline and last clinical assessment BMIs were 38.2 kg/m 2 and 35.8 kg/m 2 respectively (p<0.001), representing a median weight loss of 5.1%. At baseline, at least one metabolic parameter was abnormal in 66% of women. Total pregnancy rate was 53%. The majority of women (63%) who achieved pregnancy did so with weight loss and metabolic stabilization alone (11%) or combined with metformin (36%) and/or oral ovulation drugs (16%). Normal vitamin D (p<0.001) and triglyceride levels (p<0.05) as well as lower BMI after weight loss (p<0.05) were associated with an increased relative risk of pregnancy. CONCLUSION: Replete vitamin D status, weight loss of 5% and lower BMI as well as normal triglyceride level are significant and independent predictors of pregnancy in obese women presenting to our fertility center. The metabolic global approach is an effective program to detect metabolic abnormalities and improve obese women's pregnancy rate.

Cryopreserved embryo replacement is associated with higher birthweight compared with fresh embryo: multicentric sibling embryo cohort study.

Birth weight (BW) is higher after frozen embryo transfer (FET) than after fresh embryo replacement. No study has compared the BW of siblings conceived using the same oocyte/embryo cohort. The aim of this study was to determine whether the freezing-thawing procedure is involved in such difference. Multicenter study at Montpellier University Hospital, Clinique Ovo, Canada and Grenoble-Alpes University Hospital. The first cohort (Fresh/FET) included in vitro fertilization (IVF) cycles where the older was born after fresh embryo transfer (n = 158) and the younger after transfer of frozen supernumerary embryos (n = 158). The second cohort (FET/FET) included IVF cycles where older and younger were born after FET of embryos from the same cohort. The mean adjusted BW of the FET group was higher than that of the fresh group (3508.9 ± 452.4 g vs 3237.7 ± 463.3 g; p < 0.01). In the FET/FET cohort, the mean adjusted BW was higher for the younger by 93.1 g but this difference is not significant (3430.2 ± 347.6 g vs 3337.1 ± 391.9 g; p = 0.3789). Our results strongly suggest that cryopreservation is directly involved in the BW variation. Comparing BW difference between Fresh/FET cohort and FET/FET one, it suggests that parity is not the only responsible, increasing the role of cryopreservation step in BW variation.

Live birth rates remain stable in modified natural IVF despite low anti-Müllerian hormone: analysis of 638 cycles.

RESEARCH QUESTION: Do live birth rates (LBR) following modified natural IVF (mnIVF) differ according to serum anti-Müllerian hormone (AMH) concentration? DESIGN: Retrospective cohort study including 638 women aged ≤39 years starting their first mnIVF cycle at a university-affiliated private IVF centre. Patients were divided into three groups, by concentration of AMH: ≤0.5 ng/ml (25th percentile), 0.51-2.03 ng/ml (25-75th percentile, reference) and 2.04-6.56 ng/ml (75th percentile). Analyses were stratified by AMH percentile and the age of patients (<35, 35-39 years). Logistic regression assessed the impact of age and AMH percentile on outcomes. LBR was the primary outcome measure. RESULTS: LBR per started cycle were comparable across AMH percentiles (11.6%, 12.4% and 17.0% for the 25th, 25-75th and 75th percentile, respectively). No statistically significant difference was found between the three AMH groups with respect to cancellation, successful egg retrieval, embryo transfer, or biochemical and clinical pregnancy rates. Logistic regression analysis did not identify AMH percentile as a significant predictor of live birth. Compared with the reference group, the odds ratios (OR [95% confidence interval, CI]) for live birth in the <25th and >75th AMH percentile groups were 0.97 (0.54-1.76) and 1.41 (0.82-2.41), respectively. The results were the same regardless of age group (<35 years, 35-39 years). CONCLUSIONS: Serum AMH cannot be used to predict mnIVF outcomes. Patients in lower/upper AMH percentiles showed pregnancy and LBR comparable to patients with normal AMH.

Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial.

RESEARCH QUESTION: Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)? DESIGN: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC. RESULTS: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates. CONCLUSION: This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducted.

Tri-directional anaphases as a novel chromosome segregation defect in human oocytes.

STUDY QUESTION: What are the chromosome segregation errors in human oocyte meiosis-I that may underlie oocyte aneuploidy? SUMMARY ANSWER: Multiple modes of chromosome segregation error were observed, including tri-directional anaphases, which we attribute to loss of bipolar spindle structure at anaphase-I. WHAT IS KNOWN ALREADY: Oocyte aneuploidy is common and associated with infertility, but mechanistic information on the chromosome segregation errors underlying these defects is scarce. Lagging chromosomes were recently reported as a possible mechanism by which segregation errors occur. STUDY DESIGN, SIZE, DURATION: Long-term confocal imaging of chromosome dynamics in 50 human oocytes collected between January 2015 and May 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Germinal vesicle (GV) stage oocytes were collected from women undergoing intracytoplasmic sperm injection cycles and also CD1 mice. Oocytes were microinjected with complementary RNAs to label chromosomes, and in a subset of oocytes, the meiotic spindle. Oocytes were imaged live through meiosis-I using confocal microscopy. 3D image reconstruction was used to classify chromosome segregation phenotypes at anaphase-I. Segregation phenotypes were related to spindle dynamics and cell cycle timings. MAIN RESULTS AND THE ROLE OF CHANCE: Most (87%) mouse oocytes segregated chromosomes with no obvious defects. We found that 20% of human oocytes segregated chromosomes bi-directionally with no lagging chromosomes. The rest were categorised as bi-directional anaphase with lagging chromosomes (20%), bi-directional anaphase with chromatin mass separation (34%) or tri-directional anaphase (26%). Segregation errors correlated with chromosome misalignment prior to anaphase. Spindles were tripolar when tri-directional anaphases occurred. Anaphase phenotypes did not correlate with meiosis-I duration (P = 0.73). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Oocytes were recovered at GV stage after gonadotrophin-stimulation, and the usual oocyte quality caveats apply. Whilst the possibility that imaging may affect oocyte physiology cannot be formally excluded, detailed controls and justifications are presented. WIDER IMPLICATIONS OF THE FINDINGS: This is one of the first reports of live imaging of chromosome dynamics in human oocytes, introducing tri-directional anaphases as a novel potential mechanism for oocyte aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by grants from Fondation Jean-Louis Lévesque (Canada), CIHR (MOP142334) and CFI (32711) to GF. JH is supported by Postdoctoral Fellowships from The Lalor Foundation and CIHR (146703). The authors have no conflict of interest.

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination.

AIM: To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. METHODS: Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). RESULTS: Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. CONCLUSION: In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates.

Human S100A10 plays a crucial role in the acquisition of the endometrial receptivity phenotype.

In assisted reproduction, about 30% of embryo implantation failures are related to inadequate endometrial receptivity. To identify molecules involved in endometrial receptivity acquisition, we investigated, using a SELDI-TOF approach, the protein expression profile of early-secretory and mid-secretory endometrium samples. Among the proteins upregulated in mid-secretory endometrium, we investigated the function of S100A10 in endometrial receptivity and implantation process. S100A10 was expressed in epithelial and stromal cells of the endometrium of fertile patients during the implantation windows. Conversely, it was downregulated in the mid-secretory endometrium of infertile patients diagnosed as non-receptive. Transcriptome analysis of human endometrial epithelial and stromal cells where S100A10 was silenced by shRNA revealed the deregulation of 37 and 256 genes, respectively, related to components of the extracellular matrix and intercellular connections. Functional annotations of these deregulated genes highlighted alterations of the leukocyte extravasation signaling and angiogenesis pathways that play a crucial role during implantation. S100A10 silencing also affected the migration of primary endometrial epithelial and stromal cells, decidualization and secretory transformation of primary endometrial stromal cells and epithelial cells respectively, and promoted apoptosis in serum-starved endometrial epithelial cells. Our findings identify S100A10 as a player in endometrial receptivity acquisition.

Chronic endometritis in women with recurrent pregnancy loss and recurrent implantation failure: prevalence and role of office hysteroscopy and immunohistochemistry in diagnosis.

OBJECTIVE: To determine the prevalence of chronic endometritis (CE) in patients with recurrent implantation failure (RIF) after IVF and unexplained recurrent pregnancy loss (RPL). DESIGN: Prospective observational study between November 2012 and March 2015. SETTING: University-affiliated private IVF clinic. PATIENT(S): Women with RIF after IVF (group 1) and unexplained RPL (group 2). INTERVENTION(S): Office hysteroscopy followed by an endometrial biopsy was performed as part of the workup for RIF and RPL. The diagnosis of CE was histologically confirmed using immunohistochemistry stains for syndecan-1 (CD138). MAIN OUTCOME MEASURE(S): The prevalence of CE in each group and the sensitivity/specificity of office hysteroscopy in the diagnosis of CE. RESULT(S): Ninety-nine patients were included (46 in group 1 and 53 in group 2). The mean age was 36.3 ± 4.9 years in group 1 and 34.5 ± 4.9 years in group 2. Five biopsies were uninterpretable (three in group 1 and two in group 2) because of insufficient specimen. The prevalence of CE was 14% (6/43) in group 1 and 27% (14/51) in group 2. The sensitivity and specificity of office hysteroscopy in the diagnosis of CE were 40% (8/20) and 80% (59/74), respectively. CONCLUSION(S): We found a high prevalence of immunohistochemically confirmed CE in women with RIF and RPL. Office hysteroscopy is a useful diagnostic tool but should be complemented by an endometrial biopsy for the diagnosis of CE. CLINICAL TRIAL REGISTRATION NO: NCT01762098.

450 IU versus 600 IU gonadotropin for controlled ovarian stimulation in poor responders: a randomized controlled trial.

OBJECTIVE: To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response. DESIGN: Prospective randomized controlled nonblinded study. SETTING: University-affiliated private IVF center. PATIENT(S): Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤ 8, or a previous IVF cycle with ≥ 300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes. INTERVENTION(S): A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved. RESULT(S): The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively. CONCLUSION(S): Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response. CLINICAL TRIAL REGISTRATION NUMBER: NCT00971152.

Outcomes of 1503 cycles of modified natural cycle in vitro fertilization: a single-institution experience.

PURPOSE: A retrospective cohort study was conducted in a single academic center to determine if modified natural cycle in vitro fertilization (mnIVF) is an acceptable treatment for the infertile couple. METHODS: Cycles performed between July 2005 and December 2011 were included. In our center's mnIVF protocol, a GnRH antagonist, gonadotrophin, as well as Indocid are given on a daily basis from detection of a dominant follicle until ovulation induction. The primary outcomes were clinical pregnancy rates (CPR) per cycle started and per embryo transfer (ET). Outcomes were stratified by female patient age (≤35 years and ≥36 years). They were further stratified in each age group by ovarian response status according to the 2011 Bologna criteria. RESULTS: A total of 1503 cycles of mnIVF, performed in 782 patients, were analyzed. CPRs were 13.7 % per started cycle and 32.5 % per ET. Stratification by ovarian response status (normal or poor) in each age group showed similar CPRs in patients ≤35 years (p = 0.373), and divergent CPRs per ET in patients ≥36 years old (26.26 vs 6.25 %). CONCLUSION: MnIVF is an acceptable treatment option for patients considering IVF, particularly for women ≤35 years old and for women ≥36 years old with normal ovarian response.

Testicular sperm aspiration for nonazoospermic men: sperm retrieval and intracytoplasmic sperm injection outcomes.

OBJECTIVE: To evaluate testicular sperm aspiration (TESA) sperm retrieval rates and intracytoplasmic sperm injection outcomes in nonazoospermic men. MATERIALS AND METHODS: Data were collected retrospectively from 54 consecutive, nonazoospermic, infertile men who underwent TESA between March 2007 and September 2012. Sperm retrieval rates and clinical pregnancy outcomes were recorded. Patients were subgrouped based on clinical diagnosis: group 1, anejaculation (primary, situational); group 2, idiopathic severe oligoasthenozoospermia; and group 3, severe oligoasthenozoospermia after vasovasostomy. RESULTS: Mean (± standard deviation) paternal and maternal ages were 39 ± 7 and 35 ± 5 years, respectively. Using TESA, sperm recovery was successful in 94% (51 of 54) of the men overall and in 100% (17 of 17) of the men in group 1, 90% (28 of 31) in group 2, and 100% (6 of 6) in group 3. Overall, 35% of the couples achieved a clinical pregnancy using TESA sperm (with a mean of 1.7 ± 0.9 embryos transferred per cycle). The clinical pregnancy rates were 40% in group 1, 33% in group 2, and 33% in group 3 with no significant difference in paternal or maternal age between groups. CONCLUSION: The data indicate that TESA yields high sperm retrieval rates in select groups of nonazoospermic infertile men, and this approach results in acceptable pregnancy rates regardless of the male infertility etiology. Randomized controlled trials comparing ejaculated vs testicular sperm are needed to assess the true benefit of TESA-intracytoplasmic sperm injection in these couples.

Posthumous reproduction with surplus in vitro fertilization embryos: a study exploring users' choices.

OBJECTIVE: To report results of analysis of in vitro fertilization (IVF) users' choices regarding the potential use of their surplus cryopreserved embryos for posthumous assisted reproduction (PAR). DESIGN: Examination of signed consent forms. SETTING: Public IVF clinic. PATIENT(S): A total of 498 individuals who had signed consent forms for cryopreservation of surplus embryos. INTERVENTION(S): Content analysis of consent form. MAIN OUTCOME MEASURE(S): Agreement to PAR; importance of appropriate counseling within the consent process. RESULT(S): Approximately 68% of individuals consented to the use of surplus embryos for embryologist training and improvement of assisted reproductive techniques, and 56% consented to the use of surplus embryos in a research project; 73.5% of men and 61.8% of women agreed to leave their cryopreserved embryos to their partners for reproductive use in the event of their death. CONCLUSION(S): Our results demonstrate that a majority of both men and women agree to leave their frozen embryos to their partners for PAR in a "real life" context, i.e., in which they were required to provide consent for this prospective option. PAR involves complex issues, including the psychologic aspects of initiating a pregnancy while mourning the loss of a loved one or the effect on the prospective child. We argue that in light of the acceptability of PAR-as demonstrated by our results-further research is required regarding how to best counsel and inform IVF users about the choices they are making in this context, to ensure that their consent for PAR is in fact well informed.

Anti-Müllerian hormone (AMH): a reliable biomarker of oocyte quality in IVF.

PURPOSE: To evaluate the impact of serum AMH levels on stimulated IVF implantation and clinical pregnancy rates. METHODS: • DESIGN: Retrospective study with multivariate analysis. • SETTING: Clinique ovo (Montreal University affiliated Center). • PATIENT(S): Six hundred and thirty seven patients undergoing a stimulated IVF protocol were included. Only non-polycystic ovary patients at their first IVF attempt were considered for the analysis. • INTERVENTION(S): None. • MAIN OUTCOME MEASURES(S): Implantation and ongoing pregnancy rates. RESULT(S): Cycle outcomes were analysed according to AMH percentiles based on the AMH normogram per patient's age of our infertile population. Multivariate analyses were done to adjust for potential confounding factors such as age, total exogenous FSH dosage and number of eggs retrieved. Compared to the reference population, a significant lower mean implantation rate (0.26 vs 0.45) was observed in patients under 35 years of age with AMH < 1 ng/ml. Women with AMH < 25th percentile had less chances of having an embryo transferred, lower chances of having an ongoing pregnancy per started IVF cycle and a lower embryo freezing rate compared to the reference population. CONCLUSION(S): Patients with AMH < 0.47 ng/ml should be advised before starting a stimulated IVF cycle of the poorer prognosis compared to our reference population independently of their age, total exogenous FSH dosage and number of eggs retrieved. Therefore, AMH could enable a more individualized number of embryo transfer policy based on oocyte quality.

Sperm DNA and chromatin integrity in semen samples used for intrauterine insemination.

BACKGROUND: Sperm DNA damage is associated with male infertility but whether normozoospermic infertile men also have DNA damage is unknown. OBJECTIVE: To evaluate sperm DNA and chromatin integrity in men with mild male factor infertility. DESIGN, SETTING AND PARTICIPANTS: Prospective study of 102 consecutive men (78 normozoospermic, 15 asthenozoospermic, 9 oligozoospermic) enrolled for intrauterine insemination (IUI) and 15 fertile controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standard semen parameters and sperm chromatin and DNA integrity were assessed and compared between groups. Sperm chromatin quality was assessed by (1) aniline blue staining (AB is specific to histone lysines), (2) iodoacetamide fluorescein fluorescence (IAF targets free protamine sulfhydryl groups) and (3) sperm chromatin structure assay (SCSA) with the results expressed as % DNA fragmentation index (%DFI). RESULTS AND LIMITATIONS: The mean (±SD) percentage of spermatozoa with positive IAF fluorescence was significantly higher in the IUI population compared to fertile controls (17 % ± 10 % vs. 8 % ± 6 %, P = 0.0011) and also in the normozoospermic subset (n = 78) compared to controls (16 % ± 9 % vs. 8 % ± 6 %, P < 0.0001, ANOVA). We also observed a trend toward lower %progressive motility, and higher %AB staining and %DFI in the IUI group compared to controls. We observed significant relationships between sperm %DFI and progressive motility (r = -0.40, P < 0.0001) and between positive AB staining and IAF fluorescence (r = 0.58, P < 0.0001). CONCLUSIONS: The data indicate that sperm chromatin integrity may be abnormal in men enrolled in IUI treatment cycles, despite the fact that most of these men are normozoospermic.

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age.

BACKGROUND: Sperm DNA damage is associated with male infertility, lower pregnancy rates and pregnancy loss. OBJECTIVE: The primary aim of our study was to evaluate the prevalence of sperm DNA damage in younger and older men with normozoospermia. DESIGN, SETTING AND PARTICIPANTS: We obtained semen from 277 consecutive non-azoospermic men presenting for sperm DNA testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome measures included sperm % DNA fragmentation index (%DFI, using sperm chromatin structure assay), sperm concentration, motility and morphology, and, paternal age. RESULTS AND LIMITATIONS: Sperm % DFI was positively correlated with paternal age (r = 0.20, P < 0.001) and inversely correlated % progressive motility (r = -0.16, P = 0.01). Sperm %DFI was significantly higher in older (≥40 years) compared to younger (<40 years) normozoospermic men (17 ± 13 vs. 12 ± 8, respectively P = 0.008), whereas, sperm concentration, progressive motility and morphology were not significantly different in these two groups. Moreover, the prevalence of high levels of sperm DNA damage (>30 % DFI) was significantly higher in older compared to younger normozoospermic men (17 % vs. 3 %, respectively, P < 0.001). CONCLUSION: The data indicate that a conventional semen analysis can often fail to detect a defect in spermatogenesis (high %DFI) in older men and suggest that infertile couples with advanced paternal age, including those with normal semen parameters, should consider sperm DNA testing as part of the couple evaluation.