The Blastulation Rate Is Negatively Associated With Euploid Rate.

OBJECTIVES: To study the association between the blastulation rate, the presence of 1 pronucleus (1PN) zygotes, and the ploidy of the cohort of blastocysts. METHODS: A cross-sectional study using the existing databases of 2 university fertility centres in Canada. We included 345 cycles from 235 couples who underwent next-generation sequencing preimplantation genetic testing for the detection of aneuploidy in the study. RESULTS: A total of 1456 blastocysts were biopsied. In multivariate analysis, only female age and the number of 1PN/2PN embryos showed a negative association with euploid ratio. Surprisingly, when the analysis was limited to cycles with no delayed blastulation, the blastulation rate was also negatively associated with the euploid ratio. CONCLUSIONS: This study sheds some light on the stages of early embryo development. Further study on the mechanisms governing embryo development and the different cell cycle checkpoints in embryo development is warranted.

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.

A low total motile sperm count in donor sperm obtained from commercial banks does not affect pregnancy rates from intrauterine insemination.

Objective: Women are often concerned about the absolute quantity and quality of sperm in a thawed donor sample at the time of intrauterine insemination (IUI). The aim of this study was to determine how the total motile sperm count (TMSC) of donor sperm obtained from commercial sperm banks affects the pregnancy rate after IUI. Study design: We performed a retrospective cohort study including single women and women in same-sex relationships undergoing IUI at a single academic fertility center between January 2011 and March 2018. Our primary outcome was pregnancy rates per IUI cycle, stratified by post-washed TMSC. The data was analyzed according to TMSC and included three different groups: samples with a TMSC less than 5 million; TMSC of 5-10 million; and a TMSC greater than 10 million. Pregnancies were defined by a serum Beta-human chorionic gonadotropin (Beta-HCG) of greater than 5 mIU/mL. Chi-squared analyses and correlation coefficients were performed. Results: Overall, 9341 IUIs were conducted during the study period. Of these, 1080 (11.56%) were performed for single women and women in a same-sex relationship using commercially available donor sperm. We found that there were no differences in the pregnancy rates per insemination based on TMSC. The pregnancy rates per cycle were 15/114 (13.3%) for the group with a TMSC of less than 5 million; 34/351(9.5%) with a TMSC of 5-10 million; and 61/609 (10.0%) for samples with a TMSC greater than 10 million (p = 0.52). We found an insignificant correlation (r = -0.072) between donor sperm TMSC and pregnancy after IUI (p = 0.46). Furthermore, a reassuring beta-HCG level (>100IU/L) drawn 16 days after IUI was unrelated to TMSC (r = 0.0071, p = 0.94). Conclusion: The pregnancy rate following IUI is unaffected by the TMSC of commercially available donor sperm. This result is useful in reassuring patients when freshly thawed donor sperm is found to have a lower TMSC. Frozen sperm samples from commercial banks typically represent just a portion of an ejaculate produced by a donor who meets the banks' standards for age, health and sperm quality. As such, exaggerated sperm death caused by freezing does not result in worse outcomes with donor sperm.

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.

PROBLEM: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial. The goal of our study was to evaluate our center's 6 year-outcomes and to develop a framework for IVIg use in RPL. METHOD OF THE STUDY: Retrospective, single-center cohort study. All patients having received IVIg for unexplained RPL at the McGill Reproductive Immunology Clinic (MRIC) from January 2014 to December 2020 were included if maternal age was <42 years, body mass index (BMI) < 35 kg/m2 , non-smoker and having had ≥3 consecutive RPL despite previous treatment with aspirin and progesterone. IVIg 0.6-0.8 g/kg was given prior to conception and monthly during pregnancy until 16-20 weeks' gestation. We compared IVIg treated patient's outcomes to a separate "natural history cohort". This cohort was composed of patients consulting at the McGill recurrent pregnancy loss clinic and the MRIC over a 2-year period (January 2020 to December 2021) with similar inclusion criteria as the treatment cohort but did not receive IVIg or other immunomodulatory treatments. The association of IVIg with outcomes (compared to no IVIg) was evaluated among the groups of patients with primary RPL and secondary RPL. The primary outcome was live birth rate (LBR), secondary outcomes included IVIg safety, obstetrical, and neonatal complications. RESULTS: Among 169 patients with unexplained RPL that were included in the study, 111 had primary RPL (38 exposed to IVIg and 83 controls) and 58 had secondary RPL (nine exposed to IVIG and 49 controls). Among patients with primary RPL (n = 111), the LBR was 64.3% (18/28) among patient exposed to IVIg compared to 43.4% (36/83) in controls (p = 0.079); regression analysis adjusting for BMI and number of previous miscarriages showed benefit favoring the use of IVIg (OR = 3.27, CI 95% (1.15-10.2), p = 0.03) when evaluating for live birth. In the subgroup of patients with ≥5 previous RPL and primary RPL (n = 31), IVIg was associated with higher LBR compared to control (10/15 (66.7%) vs. 3/16 (18.8%); p = 0.0113) but not the in the sub-group of patients with <5 miscarriages and primary RPL (8/13 (61.5%) vs. 33/67 (49.3%); p = 0.548). IVIG treatment did not improve LBR in patients with secondary RPL in our study (3/9 (33.3%) vs. 23/49 (47%); p = 0.495). There were no serious adverse events in the IVIg treatment group, obstetrical/neonatal complications were similar between groups. CONCLUSION: IVIg may be an effective treatment for patients with RPL if appropriately used in specific groups of patients. IVIg is a blood product and subject to shortages especially with unrestricted off-label use. We propose considering IVIg in well-selected patients with high order RPL who have failed standard medical therapy. Further mechanistic studies are needed to understand immune-mediated RPL and IVIg's mode of action. This will enable further refinement of treatment criteria and the development of standardized protocol for its use in RPL.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

In brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Estimation of follicular growth-widely used, seldom studied.

We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in intrauterine insemination (IUI) cycles. Patient and cycle characteristics were extracted from an existing database. Comparisons were made between the pregnant (defined as a positive beta hCG) and non-pregnant groups for the following variables: patient's age, number of previous IUI cycles, type of ovarian stimulation, endometrial thickness, number of follicles measuring 14 mm and above, pre and post wash sperm parameters, cycle day when IUI was done and number of days between last ultrasound scan and ovulation trigger. A total of 7302 cycles were included in the final analysis. In 4055 cycles (55.5%) the hCG trigger was on the day of the last ultrasound, in 2285 cycles (31.3%) the hCG trigger was 1 day after the last ultrasound, in 850 (11.6%) it was 2 days after the last ultrasound and in 112 (1.5%) it was 3 or more days after the last ultrasound. Sperm parameters, younger maternal age, and the number of follicles above 14 mm were all associated with pregnancy. No association was found between positive pregnancy test rates and the time from last ultrasound to hCG trigger. Planning IUI based on the estimation of follicular growth 1-4 days before trigger, does not affect pregnancy rates.

The influence of regulation of medically assisted reproduction on the risk of hospitalization in the first 2 years of life.

STUDY QUESTION: Do publicly funded fertility treatment and single embryo transfer (SET) result in lower hospitalization rates of children of parents with infertility? SUMMARY ANSWER: Following the 2010 Quebec law introducing free fertility treatment and SET, neonatal intensive care unit (NICU) admissions decreased among all children born to parents with infertility, but not among singletons, whose risk remained slightly higher than that of children of parents without infertility, even accounting for treatment and maternal age. WHAT IS KNOWN ALREADY: Previous studies reported lower NICU admission rates among children conceived with ART after the 2010 law; however, children conceived without ART by parents with infertility were not considered. STUDY DESIGN, SIZE, DURATION: Cohort study of children born in 1997-2017 to patients evaluated for infertility ('exposed') at an academic fertility center in Montreal (Canada) in 1996-2015. A random sample of births to Montreal residents served as comparison. Outcomes were identified from Quebec administrative databases. PARTICIPANTS/MATERIALS, SETTING, METHODS: We compared children's healthcare utilization before and after the 2010 law in 6273 exposed and 12 583 randomly sampled births (6846 and 12 775 children, respectively). We repeated the analysis among children conceived in the 63 months before and after the law ('restricted period'), and examined whether differences in twinning, fertility treatment, and maternal age explained the higher risk of NICU admission among children of parents with infertility. MAIN RESULTS AND THE ROLE OF CHANCE: In the exposed cohort, the proportion of twin births and of several adverse outcomes declined after the law. NICU admission and duration of NICU stay decreased overall, but not in singletons. Both measures remained higher in exposed children. Except for NICU admission, hospitalization rates were similar in exposed and random sample children. After accounting for fertility treatment and maternal age, exposed singletons were 17% more likely to be admitted to the NICU than children of parents with no medical history of infertility. LIMITATIONS, REASONS FOR CAUTION: Sample size was relatively small; infertile patients were from a single center and the random sample from one city. Despite some limitations, administrative databases are likely to accurately reflect healthcare utilization. WIDER IMPLICATIONS OF THE FINDINGS: Universal access to treatment and, particularly, SET results in an overall reduction of adverse outcomes among children conceived with treatment; however, children of parents with infertility are at a slightly higher risk, regardless of treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Canadian Institutes for Health Research (CIHR, grant no. 123362). No competing interests. TRIAL REGISTRATION NUMBER: N/A.

A comparison of frozen-thawed embryo transfer protocols in 2920 single-blastocyst transfers.

OBJECTIVE: To assess the effect of frozen-thawed embryo transfer (FET) protocol on live-birth rate (LBR) and clinical pregnancy rate (CPR), in single-vitrified-blastocyst transfer MATERIALS AND METHODS: Retrospective cohort study with FET of a single-blastocyst embryos (n = 2920 cycles) thawed 2013-2018. FET protocols were natural cycles (NC-FET) (n = 147), artificial hormone replacement treatment cycles (HRT-FET) (n = 2645), and modified NC (mNC) with hCG triggering (n = 128). Primary outcome was LBR. Adjustment for age, embryo grade, year of freezing\thawing, infertility cause, and endometrial thickness was performed. RESULTS: There were no significant differences between the groups with regard to female age, embryo grade, and endometrial thickness. LBR was higher in the mNC compared to HRT-FET cycles (38.3% vs. 20.9% P < 0.0001), and in the NC compared to HRT-FET cycles (34.7% vs. 20.9%, P = 0.0002). CPR was higher in the mNC compared to HRT-FET cycles (46.1% vs. 33.3% P = 0.0003), and in the NC compared to HRT-FET cycles (45.9% vs. 33.3%, P = 0.002). There was no significant difference in LBR or CPR between NC-FET and mNC-FET. Higher LBR with NC-FET and mNC-FET remained significant after adjusting for confounders (aOR 2.42, 95%CI 1.53-3.66, P < 0.0001). CONCLUSION: The use of the convenient artificial HRT-FET cycles must be cautiously reconsidered in light of the potential negative effect on LBR when compared with natural cycle FET.

Is There an Association Between Sperm Parameters and Sexual Orientation? A Cross Sectional Study.

OBJECTIVE: To evaluate whether sexual orientation affects sperm parameters. METHODS: This was a cross-sectional study using existing data from an academic reproductive centre for the period of April 01, 2009, to March 31, 2021. We compared the results of sperm analysis from male patients who were in same-sex relationships (study group) with those of men in heterosexual relationships who did not have male-factor infertility (control group). A subsequently comparison of both groups with World Health Organization (WHO) reference values was also performed. RESULTS: Thirty-nine samples from the study group were compared with 494 samples from the control group. All parameters, apart from morphology, were comparable. The median sperm concentrations were 64 (interquartile range [IQR] 32.1-102.9) million/mL and 50.1 (IQR 25.3-92.5) million/mL in the study and control groups, respectively (P = 0.252), whereas the median percentage of progressive motile sperm was 50% (IQR 34-65) in the study group and 52% (IQR 33-65) in the control group (P = 0.198). The median percentage of morphologically normal sperm was higher in the control group than in the study group (6% vs. 5%; P = 0.019). However, no significant difference was found when sperm morphology was dichotomized with the cut-off of ≥4% (74.1% and 74.4%, respectively; P = 0.966). When compared with the WHO reference group, the percentage of men with total motile sperm counts ≥10 million and the percentage of men with normal morphology were significantly lower in both groups. CONCLUSION: Our study suggests that there is no relationship between sexual orientation and sperm parameters.

MYO10 promotes transzonal projection-dependent germ line-somatic contact during mammalian folliculogenesis†.

Granulosa cells of growing ovarian follicles elaborate filopodia-like structures termed transzonal projections (TZPs) that supply the enclosed oocyte with factors essential for its development. Little is known, however, of the mechanisms underlying the generation of TZPs. We show in mouse and human that filopodia, defined by an actin backbone, emerge from granulosa cells in early stage primary follicles and that actin-rich TZPs become detectable as soon as a space corresponding to the zona pellucida appears. mRNA encoding Myosin10 (MYO10), a motor protein that accumulates at the base and tips of filopodia and has been implicated in their initiation and elongation, is present in granulosa cells and oocytes of growing follicles. MYO10 protein accumulates in foci located mainly between the oocyte and innermost layer of granulosa cells, where it colocalizes with actin. In both mouse and human, the number of MYO10 foci increases as oocytes grow, corresponding to the increase in the number of actin-TZPs. RNAi-mediated depletion of MYO10 in cultured mouse granulosa cell-oocyte complexes is associated with a 52% reduction in the number of MYO10 foci and a 28% reduction in the number of actin-TZPs. Moreover, incubation of cumulus-oocyte complexes in the presence of epidermal growth factor, which triggers a 93% reduction in the number of actin-TZPs, is associated with a 55% reduction in the number of MYO10 foci. These results suggest that granulosa cells possess an ability to elaborate filopodia, which when directed toward the oocyte become actin-TZPs, and that MYO10 increases the efficiency of formation or maintenance of actin-TZPs.

Hereditary breast cancer and fertility preservation outcomes.

PURPOSE: To determine the frequency of hereditary breast cancer associated with different mutated genes and to evaluate fertility preservation (FP) outcomes among young women with hereditary breast cancer when compared to non-hereditary breast cancer. MATERIAL AND METHODS: A retrospective cohort study of women with breast cancer who underwent fertility preservation treatment at our academic fertility center between 2005 and 2019. We included all women with breast cancer aged < 40 years who had a genetic testing and underwent fertility preservation before starting gonadotoxic therapy (n = 132). Our objective was to evaluate the total number of oocytes retrieved, mature oocytes MII, embryos (where appropriate), cryopreserved oocytes, and/or embryos. RESULTS: Of 132 women with breast cancer, 40 women were found to be genetically positive (31.4%), 31 women of 40 (77.5%) had a BRCA mutation, 3 (7.5%) had ATM, 2 (5%) had CHK2, and one (2.5%) for each of the following genes: PALP2, NF, MUTYH.c.536A, and TP53. There was no significant difference between the groups in the total number of eggs retrieved and the number of MII oocytes and cryopreserved oocytes. The numbers of fertilized oocytes and cryopreserved embryos in the hereditary (n = 40) and non-hereditary (n = 92) group were (5.15 ± 6.6 vs 2.90 ± 4.2, P = 0.054) and (3.35 ± 3.7 vs 1.9 ± 2.8, P = 0.046) respectively. CONCLUSION: More than three quarters of positive mutated genes in women with breast cancer are BRCA mutations. Compared to those with non-hereditary breast cancer, women with hereditary breast cancer attained higher number of cryopreserved embryos.

Effects of embryo retention during embryo transfer on IVF outcomes.

PROPOSE: To investigate embryo retention (ER) rate in embryo transfer (ET) cycles and its effects on reproductive outcomes in a large database. METHODS: A matched retrospective cohort study in a tertiary academic hospital-based reproductive center. A total of 15,321 ET cycles were performed from January 2008 to December 2018. Each woman was matched with three separate control subjects of the same age (± 1 year), embryo condition, main causes of infertility, and type of protocol used for fresh or frozen ET cycles. The main outcomes were ER rate, and implantation, clinical pregnancy, ectopic pregnancy, and live birth rates. RESULTS: The overall incidence of ER was 1.4% (213/15,321). There was no difference in the rate of ER rate in fresh ET cycles compared with frozen transfer cycles (P = 0.54). We matched 188/213 (88%) of cases in the ER group to 564 non-ER cases. There were no cases of the blood in the catheter seen in the ER group. Pregnancy outcomes were similar between the ER and the non-ER cycles: clinical pregnancy rate (31.3% vs. 36.1%, P = 0.29), implantation rate (26.2% vs. 31.3%, P = 0.2), live birth rate (20.3% vs. 24%, P = 0.53), ectopic pregnancy rate (0.5% vs. 0.4%, P = 0.18), and miscarriage rate (10.7% vs. 11.3%, P = 0.53). CONCLUSION: Our results suggest that ER rate does not affect the reproductive outcomes including clinical pregnancy rate, implantation rate, and live birth rate. Patients and physicians should not be concerned about the retention of embryos during transfer since there is no effect on pregnancy outcome.

Does increasing estrogen dose during frozen embryo transfer affect pregnancy rate?

OBJECTIVE: To assess the effect of increasing estrogen doses during hormone therapy frozen embryo transfer (HT-FET) cycles on endometrial thickness and success rates compared to patients who received fixed estrogen dose. MATERIALS AND METHODS: A retrospective study from a university-based fertility clinic during the years 2008-2021. We compared two groups: the fixed-dose group (i.e., received 6 mg estradiol dose daily until embryo transfer) and the increased-dose group (i.e., the initial estradiol dose was 6 mg daily, and was increased during the cycle). PRIMARY OUTCOME: clinical pregnancy rate. RESULTS: The study included 5452 cycles of HT-FET: 4774 cycles in the fixed-dose group and 678 cycles in the increased-dose group. Ultrasound scan on days 2-3 of the cycle showed endometrial thickness slightly different between the two groups (4.2 mm in the fixed-dose and 4.0 mm in the increased-dose group, P = 0.003). The total estrogen dose was higher, and the treatment duration was longer in the increased than the fixed-dose group (122 mg vs. 66 mg and 17 days vs. 11 days, respectively; P < 0.001). The last ultrasound scan done before the addition of progesterone showed that the endometrial thickness was significantly thicker in the fixed than the increased-dose group (9.5 mm vs. 8.3 mm; P < 0.001). The clinical pregnancy rates were 35.8% in the increased-group vs. 34.1% in the fixed-dose group; P = 0.401. CONCLUSIONS: The increased-dose group had thinner endometrium despite the higher doses of estrogen and longer treatment duration than the fixed-dose group. However, the pregnancy rates were similar between the two groups.

Transvaginal Sonography Post-Office Hysteroscopy as a Screening Tool for Tubal Patency: A Reliable and Feasible Technique in an Outpatient Setting.

OBJECTIVE: To determine feasibility and accuracy of post-hysteroscopic transvaginal ultrasonography (TVUS) measurement of pelvic fluid accumulation as a screening method for tubal patency (TP). METHODS: We conducted a retrospective cohort study of 85 patients who underwent uterine cavity assessment by office hysteroscopy at our university-affiliated fertility centre from November 2019 to October 2020. During the study period, two-dimensional (2D) TVUS was performed pre- and post-hysteroscopy to evaluate TP. Patient records were reviewed for demographics, diagnosis, and prior/subsequent TP testing. Predictive values for TP were calculated. RESULTS: Pelvic fluid accumulation post-hysteroscopy was found in 65.9% of patients (56). Accumulation of fluid was seen with the use of as little as 10-50 mL of saline. Using more fluid did not increase the likelihood of demonstrating TP (P = 0.17). A trend towards more false-negative results for TP was observed when less fluid was used (7.7% with 10-50 mL vs. 3.8% with 60-190 mL and 1.3% with 200-760 mL; P = 0.10). The positive predictive value (PPV) of TVUS post-hysteroscopy in comparison to known patency/occlusion was 100%; negative predictive value (NPV) was 33%; sensitivity was 82.8%; and specificity was 100%. Similar values were seen in a second analysis that included patients with highly suspected patent or occluded tubes (n = 60); presumed predictive values were: PPV 100%, NPV 42%, sensitivity 78.8%, and specificity 100%. The use of more fluid did not increase pain (P = 0.75). This finding remains after accounting for confounders (e.g., pre-medication, endometrial biopsy). CONCLUSION: TVUS pre- and post-hysteroscopy is feasible in an outpatient setting, and can serve as a reliable screening tool for TP. When hysteroscopy is performed and TP is not known, TVUS can be added for screening, potentially omitting the need for more invasive examinations. With limited non-urgent ambulatory services, it is of upmost importance to maximize information from a single procedure.

Do oral ovulation induction agents offer benefits in women 38 to 43 years of age undergoing insemination cycles?

OBJECTIVE: To compare the success of ovulation induction using oral agents versus gonadotropins (GTs) in women ≥38 years old. STUDY DESIGN: A retrospective cohort study was performed including all first to third stimulated IUI cycles conducted after the age of 38 years in a single academic fertility center between 01/2011 and 03/2018. RESULTS: A total of 1596 IUI cycles were included. 240 cycles were with clomiphene citrate (CC), 176 letrozole cycles and 1180 gonadotropin (GTs) cycles. The GTs group were older (p < 0.001), had lower antral follicular count (p < 0.001), and thicker endometrium (p < 0.001) compared to the oral agent groups. The letrozole group had a less mature follicles (p = 0.004) at the time of triggering compared to the other groups. No difference in pregnancy or clinical pregnancy rates was observed after controlling for confounders when comparing the 3-groups. 5 multiple pregnancies occurred, all in the GTs group. The groups were subdivided by age; 38-39 years old (N = 750) and 40-43 years old (N = 846). Nevertheless, no statistical difference was observed in pregnancy rates and clinical pregnancy rates between oral agents and GTs when controlling for the confounding effects among women at age 38-39 (p = 0.47, p = 1.0; respectively) and among women 40-43-years-old (p = 0.16, p = 1.0; respectively). CONCLUSIONS: Clearly costs of oral agents are lower and they are more patient friendly than GTs, therefore oral agents should be first line for ovarian stimulation and IUI in women 38-43-years of age.

Effect of embryo stage at transfer on placental histopathology features in singleton live births resulting from fresh embryo transfers.

OBJECTIVE: To evaluate the effect of embryo stage at transfer on placental histopathology and perinatal outcome in singleton live births resulting from fresh embryo transfers (ETs). DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): The study population included all live births after fresh ETs during the period from 2009 to 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes included anatomic, inflammatory, vascular malperfusion, and villous maturation placental features. Secondary outcomes included fetal, maternal, and perinatal complications. RESULT(S): A total of 677 live births were included in the final analysis and were allocated to the cleavage-stage (n = 252) and blastocyst (n = 425) ET groups. After the adjustment for confounding factors, the blastocyst group was found to be associated with a higher incidence of circummarginate membranes insertion (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.2-3.4), delayed villous maturation (OR 8.5, 95% CI 1.2-69.3), chorangiosis (OR 2.0, 95% CI 1.2-3.8), parenchymal calcifications (OR 10.6, 95% CI 1.4-80.2), and intrapartum nonreassuring fetal heart rate tracing (OR 2.4, 95% CI 1.3-4.5). Compared with cleavage-stage ETs, live births resulting from the blastocysts were associated with a lower incidence of velamentous cord insertion (OR 0.5, 95% CI 0.3-0.9), retroplacental hematoma (OR 0.3, 95% CI 0.1-0.8), subchorionic thrombi (OR 0.3, 95% CI 0.1-0.8), and avascular villi (OR 0.2, 95% CI 0.03-0.7). CONCLUSION(S): Live births resulting from fresh cleavage-stage and blastocyst ETs have different placental histopathology features, with a higher rate of intrapartum nonreassuring fetal heart rate tracing in the blastocyst group.

Is intrauterine insemination a viable treatment option for women over 43 years old? An analysis by ovarian stimulation protocol and sperm source.

PURPOSE: The aim of this study was to determine how female age at the end of the reproductive spectrum effects success of natural cycle intrauterine insemination (IUI) or IUI in combination with ovarian stimulation. METHODS: We performed a retrospective cohort study of women 43 years of age and older at the time of IUI in a single academic fertility center between January 2011 and March 2018. Primary outcomes were both pregnancies and live births per cycle of IUI. Data are presented as percentage or mean ± SD. Fisher exact and chi-squared analyses were performed. RESULTS: There were 9334 IUI cycles conducted during the study period. Of these cycles, 325 IUIs (3.5%) were for women aged 43 years and over at the time of insemination (43.6 ± 0.8, range 43 to 47 years). Analysis of these 325 IUI cycles revealed 5 biochemical pregnancies (1.5%) and only 1 live birth (0.3%). The pregnancy rate did not differ between IUIs using donor sperm (N = 1/49, 2.0%) compared to IUIs with partner sperm (N = 4/276, 1.4%). The pregnancy rate did not differ between IUIs with gonadotropins (N = 2/211, 0.9%), clomiphene or letrozole (N = 2/78, 2.6%), or natural cycle (N = 1/36, 2.8%). CONCLUSIONS: The use of intrauterine inseminations in women 43 years of age and older is an ineffective treatment strategy. This is irrespective of the use of ovarian stimulation or donor sperm. Costly gonadotropin injections did not increase the chance of pregnancy nor did oral medication when compared to natural cycle IUIs.

Effect of newborn gender on placental histopathology and perinatal outcome in singleton live births following IVF.

RESEARCH QUESTION: Does newborn gender affect placental histopathology pattern and perinatal outcome in singleton live births following IVF treatment? DESIGN: Retrospective cohort study evaluating data of all live births from one academic tertiary hospital following IVF treatment during 2009-2017. All patients had placentas sent for pathological evaluation irrelevant of maternal and fetal complications status. Exclusion criteria were abnormal uterine cavity findings, previous uterine surgery, in-vitro maturation cycles, gestational carrier cycles, oocyte recipient cycles, preimplantation genetic diagnosis cycles and multiple pregnancies. The primary outcomes included anatomical, inflammation, vascular malperfusion and villous maturation placental features. The secondary outcomes included fetal, maternal, perinatal and delivery complications. A multivariate analysis was conducted to adjust the results for factors potentially associated with placental pathology features. RESULTS: A total of 1057 live births were included in the final analysis and were allocated to the study groups according to fetal gender: males (n = 527) and females (n = 530). After adjustment for potential confounding factors, male gender was significantly associated with villous agglutination (odds ratio [OR] 9.8; 95% confidence interval [CI] 1.4-78.2), avascular villi (OR 4.1; 95% CI 1.3-12.6) and maternal vascular malperfusion (OR 1.8; 95% CI 1.2-2.7). Female gender was significantly associated with bilobed placenta (OR 0.2; 95% CI 0.06-0.8) and subchorionic thrombi (OR 0.5; 95% CI 0.3-0.9). The prevalence of adverse fetal, maternal and delivery outcomes was similar between the groups. CONCLUSIONS: Newborn gender has a significant impact on the placental histopathology pattern, which can contribute to the development of adverse perinatal outcomes.

Added Benefit of Immature Oocyte Maturation for Fertility Preservation in Women with Malignancy.

To assess the added value of maturing immature oocytes collected during fertility preservation treatments in women with malignancy. A retrospective case-control study analyzing the results of 327 cancer patients undergoing fertility preservation treatments. Oocyte maturation rates and cycle parameters were compared between 3 types of fertility preservation treatments: (1) stimulated IVF cycle (n = 143), (2) non-stimulated IVM cycle (n = 158), (3) follicle aspiration and oocyte collection from ovarian tissue prepared for ovarian tissue cryopreservation followed by in vitro maturation of the immature oocytes (n = 48). The primary outcome measure was the maturation rate and the number of mature oocytes. The secondary outcomes were oocyte fertilization and embryo development rates. The mean maturation rate in IVF cycles was 38% and in the non-stimulated IVM cycles was 55%. In women who chose to cryopreserve their embryos, similar fertilization and embryo cleavage rates were found in oocytes that matured after stimulated IVF cycles compared to non-stimulated IVM cycles. Gonadotropin-releasing hormone agonist triggering, treatment with aromatase inhibitor, or oral contraceptives use before the cycle did not affect the maturation rate. Ovarian stimulation yields the highest number of oocytes or embryos for cryopreservation. Although the maturation rate of immature oocytes collected in stimulated IVF cycles is low, it is still a viable source of oocytes that can be used to improve the efficacy of fertility preservation treatments by increasing the number of mature oocytes available for freezing or fertilization.