The physiological and pathophysiological roles of copper in the nervous system.

Copper is a critical trace element in biological systems due the vast number of essential enzymes that require the metal as a cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine-ß-hydroxylase. Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper-induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper-requiring enzymes, such as SOD1-linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.

Pregnancy outcomes after superovulation-intrauterine insemination (SO-IUI) using gonadotropins versus letrozole in the obese population.

PURPOSE: To compare fertility outcomes of obese patients (body mass index [BMI] ≥ 30 kg/m2) undergoing superovulation and intrauterine insemination (SO-IUI) using gonadotropins versus letrozole. METHODS: A single centre retrospective cohort study of obese patients undergoing SO-IUI using gonadotropins or letrozole between January/2019 and June/2022. Primary outcome was clinical pregnancy rate (intrauterine pregnancy with positive fetal heart rate). Secondary outcomes included rates of multifollicular development, multiple pregnancy, spontaneous abortion and cycle cancellation. Subgroup analysis was done stratifying by obesity class. A multivariate logistic regression model was used for primary/secondary outcomes, adjusting for clinically determined covariates. RESULTS: Out of 802 total identified SO-IUI cycles, 715 cycles were completed (518-gonadotropins and 197-letrozole cycles). The clinical pregnancy rates were not significantly different in obese patients undergoing SO-IUI with gonadotropins versus letrozole when adjusted for age, gravidity, parity, cause of infertility, IUI cycle number, endometrial thickness, sperm source and post-wash motile sperm count (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 0.72-2.59). Similarly, no significant associations were found in spontaneous abortion (aOR1.46, 95%CI 0.42-5.08), multiple pregnancy (aOR1.33, 95%CI 0.20-8.88) or cancellation rates (OR0.89, 95%CI 0.55-1.45) between the two groups. The rates of multifollicular development were also comparable between the two groups (aOR0.51, 95% CI 0.19-1.38). For cycles involving gonadotropins, higher BMI classes required higher total gonadotropin dose (p < 0.001). CONCLUSION: After adjusting for patient and cycle factors, gonadotropins and letrozole led to comparable odds of achieving pregnancy in obese patients undergoing SO-IUI. Future research in the obese population will help to better understand how to optimize fertility treatments for this growing population.

Microglial reprogramming by Hv1 antagonism protects neurons from inflammatory and glutamate toxicity.

Although the precise mechanisms determining the neurotoxic or neuroprotective activation phenotypes in microglia remain poorly characterized, metabolic changes in these cells appear critical for these processes. As cellular metabolism can be tightly regulated by changes in intracellular pH, we tested whether pharmacological targeting of the microglial voltage-gated proton channel 1 (Hv1), an important regulator of intracellular pH, is critical for activated microglial reprogramming. Using a mouse microglial cell line and mouse primary microglia cultures, either alone, or co-cultured with rat cerebrocortical neurons, we characterized in detail the microglial activation profile in the absence and presence of Hv1 inhibition. We observed that activated microglia neurotoxicity was mainly attributable to the release of tumor necrosis factor alpha, reactive oxygen species, and zinc. Strikingly, pharmacological inhibition of Hv1 largely abrogated inflammatory neurotoxicity not only by reducing the production of cytotoxic mediators but also by promoting neurotrophic molecule production and restraining excessive phagocytic activity. Importantly, the Hv1-sensitive change from a pro-inflammatory to a neuroprotective phenotype was associated with metabolic reprogramming, particularly via a boost in NADH availability and a reduction in lactate. Most critically, Hv1 antagonism not only reduced inflammatory neurotoxicity but also promoted microglia-dependent neuroprotection against a separate excitotoxic injury. Our results strongly suggest that Hv1 blockers may provide an important therapeutic tool against a wide range of inflammatory neurodegenerative disorders.

Copper induces neuron-sparing, ferredoxin 1-independent astrocyte toxicity mediated by oxidative stress.

Copper is an essential enzyme cofactor in oxidative metabolism, anti-oxidant defenses, and neurotransmitter synthesis. However, intracellular copper, when improperly buffered, can also lead to cell death. Given the growing interest in the use of copper in the presence of the ionophore elesclomol (CuES) for the treatment of gliomas, we investigated the effect of this compound on the surround parenchyma-namely neurons and astrocytes in vitro. Here, we show that astrocytes were highly sensitive to CuES toxicity while neurons were surprisingly resistant, a vulnerability profile that is opposite of what has been described for zinc and other toxins. Bolstering these findings, a human astrocytic cell line was similarly sensitive to CuES. Modifications of cellular metabolic pathways implicated in cuproptosis, a form of copper-regulated cell death, such as inhibition of mitochondrial respiration or knock-down of ferredoxin 1 (FDX1), did not block CuES toxicity to astrocytes. CuES toxicity was also unaffected by inhibitors of apoptosis, necrosis or ferroptosis. However, we did detect the presence of lipid peroxidation products in CuES-treated astrocytes, indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Indeed, treatment with anti-oxidants mitigated CuES-induced cell death in astrocytes indicating that oxidative stress is a mediator of CuES-induced glial toxicity. Lastly, prior induction of metallothioneins 1 and 2 in astrocytes with zinc plus pyrithione was strikingly protective against CuES toxicity. As neurons express high levels of metallothioneins basally, these results may partially account for their resistance to CuES toxicity. These results demonstrate a unique toxic response to copper in glial cells which contrasts with the cell selectivity profile of zinc, another biologically relevant metal.

Live birth rates after resolution of endometrial cavity fluid in frozen embryo transfer cycles.

RESEARCH QUESTION: Are live birth rates affected in frozen embryo transfer cycles that develop transient endometrial cavity fluid that resolves by day of embryo transfer? DESIGN: The first frozen blastocyst transfer cycle between January 1st, 2016 and December 31st, 2019 were included in this retrospective cohort study at an academic fertility center. The presence or absence of endometrial cavity fluid (ECF) detected on initial ultrasound and at time of transfer was recorded. Patients who had persistent ECF at time of transfer were excluded from the study. The primary outcome was live birth rate in the group with resolved ECF relative to the group without ECF. RESULTS: A total of 1034 frozen blastocyst transfer cycles were included, 54 with resolved ECF and 980 without ECF. Adjusted analyses were performed using a log-binomial regression model. Live birth rates were 35.2% and 34.2%, adjusted risk ratio 1.00 [95% CI 0.70-1.50] in the two groups, respectively. CONCLUSION: Live birth rates in frozen embryo transfer cycles are equivalent between patients with resolved endometrial cavity fluid compared to those who never had endometrial cavity fluid. Our findings suggest that the presence of endometrial cavity fluid is likely not detrimental to live birth rates if the fluid spontaneously resolves by the time of embryo transfer.

Time-lapse KIDScoreD5 for prediction of embryo pregnancy potential in fresh and vitrified-warmed single-embryo transfers.

RESEARCH QUESTION: Can KIDScoreD5 predict which blastocysts have the highest potential for achieving pregnancy? DESIGN: A retrospective cohort study of 670 single fresh or frozen (FET) embryo transfer cycles was conducted between May 2019 and June 2021 at the Ottawa Fertility Centre, Canada. Blastocysts obtained from stimulated eligible cycles and cultured in a time-lapse incubator were selected for transfer or cryopreservation based on Gardner morphological scoring. Implantation and viable pregnancy rates were analysed retrospectively using KIDScoreD5 and Gardner scores associated with the transferred embryos. The predictive power of the KIDScoreD5 and Gardner assessment was evaluated using the average area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: KIDScoreD5 was positively correlated with implantation (r = 0.96, P = 0.002) and viable pregnancy (r = 0.96, P  = 0.0001) rates. In fresh embryo transfer cycles, the AUC for implantation rate was significantly higher for KIDScoreD5 compared with Gardner scoring (0.70 versus 0.63, P  = 0.03). For FET, significantly higher AUC were calculated for KIDScoreD5 than for Gardner scoring, for both implantation (0.64 versus 0.54, P  = 0.002) and viable pregnancy (0.63 versus 0.53, P  = 0.002) rates. When the ranking of cryopreserved embryos was based on KIDScoreD5, 46.2% of the FET cycles had at least one unused sibling embryo with a better KIDScoreD5 than the one selected for FET based on Gardner assessment. CONCLUSIONS: KIDScoreD5 predicts implantation and viable pregnancy rates of blastocysts better than Gardner morphological assessment in single fresh or cryopreserved embryo transfer cycles.

Does omitting teratospermia as a selection criterion for ICSI change pregnancy rates?

PURPOSE: There is controversy whether teratospermia is associated with poorer IVF outcomes and if ICSI may overcome this deficit. The debate likely lies in study heterogeneity, poor adjustment for confounders, and inter-observer variation in sperm morphology assessment. Given the current literature, a shift in practice was implemented at our center in February 2017, whereby teratospermia was no longer a criterion for ICSI. We hypothesized that, despite decreasing ICSI rates, we would see no change in ART outcomes. METHODS: A retrospective study was performed including 1821 couples undergoing IVF/ICSI at a single center from January 2016 to December 2018, divided into cohorts before and after the practice change. The primary outcome of clinical pregnancy and secondary outcomes of fertilization, fertilization failure, good quality blastocyst formation, embryo utilization, positive hCG, and miscarriage rates was compared, adjusting for potential confounders. Subgroup analysis was performed evaluating teratospermia as the only reason for a male factor infertility diagnosis. RESULTS: Despite a decrease in ICSI rate of 30.3%, we found no significant difference in clinical intrauterine pregnancy rate, with an adjusted relative risk of 0.93 (0.81, 1.07, P = 0.3008). There were no significant differences in other secondary outcomes after multivariate adjustment. Subgroup analysis for those with male factor infertility due to teratospermia showed no difference in outcomes. CONCLUSION: This study concurs with the recent data suggesting that employing ICSI solely for teratospermia is unnecessary. This may allow clinics to decrease ICSI rates without sacrificing success rates, leading to lower cost and risk associated with treatment.

Angiotensin II mediates the axonal trafficking of tyrosine hydroxylase and dopamine ß-hydroxylase mRNAs and enhances norepinephrine synthesis in primary sympathetic neurons.

In the sympatho-adrenal system, angiotensin II (Ang II) acts as a key neuromodulatory component. At sympathetic nerve terminals, Ang II influences sympathetic transmission by enhancing norepinephrine (NE) synthesis, facilitating NE release and inhibiting NE uptake. Previously, it was demonstrated that tyrosine hydroxylase (TH) mRNA is trafficked to the distal axons of primary superior cervical ganglia (SCG) neurons, directed by a cis-acting regulatory element (i.e. zipcode) located in the 3'UTR of the transcript. Results of metabolic labeling studies established that the mRNA is locally translated. It was further shown that the axonal trafficking of the mRNA encoding the enzyme plays an important role in mediating dopamine (DA) and NE synthesis and may facilitate the maintenance of axonal catecholamine levels. In the present study, the hypothesis was tested that Ang II induces NE synthesis in rat primary SCG neurons via the modulation of the trafficking of the mRNAs encoding the catecholamine synthesizing enzymes TH and dopamine ß-hydroxylase (DBH). Treatment of SCG neurons with the Ang II receptor type 1 (AT1R) agonist, L-162,313, increases the axonal levels of TH and DBH mRNA and protein and results in elevated NE levels. Conversely, treatment of rat SCG neurons with the AT1R antagonist, Eprosartan, abolished the L-162,313-mediated increase in axonal levels of TH and DBH mRNA and protein. In a first attempt to identify the proteins involved in the Ang II-mediated axonal transport of TH mRNA, we used a biotinylated 50-nucleotide TH RNA zipcode as bait in the affinity purification of TH zipcode-associated proteins. Mass spectrometric analysis of the TH zipcode ribonucleoprotein (RNP) complex immune-purified from SCG neurons led to the identification of 163 somal and 127 axonal proteins functionally involved in binding nucleic acids, the translational machinery or acting as subunits of cytoskeletal and motor proteins. Surprisingly, immune-purification of the TH axonal trafficking complex, results in the acquisition of DBH mRNA, suggesting that these mRNAs maybe transported to the axon together, possibly in the same RNP complex. Taken together, our results point to a novel mechanism by which Ang II participates in the regulation of axonal synthesis of NE by modulating the local trafficking and expression of TH and DBH, two key enzymes involved in the catecholamine biosynthetic pathway.

The local expression and trafficking of tyrosine hydroxylase mRNA in the axons of sympathetic neurons.

Synthesis and regulation of catecholamine neurotransmitters in the central nervous system are implicated in the pathogenesis of a number of neuropsychiatric disorders. To identify factors that regulate the presynaptic synthesis of catecholamines, we tested the hypothesis that the rate-limiting enzyme of the catecholamine biosynthetic pathway, tyrosine hydroxylase (TH), is locally synthesized in axons and presynaptic nerve terminals of noradrenergic neurons. To isolate pure axonal mRNA and protein, rat superior cervical ganglion sympathetic neurons were cultured in compartmentalized Campenot chambers. qRT-PCR and RNA in situ hybridization analyses showed that TH mRNA is present in distal axons. Colocalization experiments with nerve terminal marker proteins suggested that both TH mRNA and protein localize in regions of the axon that resemble nerve terminals (i.e., synaptic boutons). Analysis of polysome-bound RNA showed that TH mRNA is present in polysomes isolated from distal axons. Metabolic labeling of axonally synthesized proteins labeled with the methionine analog, L-azidohomoalanine, showed that TH is locally synthesized in axons. Moreover, the local transfection and translation of exogenous TH mRNA into distal axons facilitated axonal dopamine synthesis. Finally, using chimeric td-Tomato-tagged constructs, we identified a sequence element within the TH 3'UTR that is required for the axonal localization of the reporter mRNA. Taken together, our results provide the first direct evidence that TH mRNA is trafficked to the axon and that the mRNA is locally translated. These findings raise the interesting possibility that the biosynthesis of the catecholamine neurotransmitters is locally regulated in the axon and/or presynaptic nerve terminal.

Early Discharge after Laparoscopic Hysterectomy: a Prospective Study.

OBJECTIVE: To evaluate the feasibility of same-day discharge after laparoscopic hysterectomy without excluding patients with complex surgical pathology and medical comorbidities. These factors are often considered potential barriers to early discharge, and the literature is lacking prospective trials addressing the feasibility of same-day discharge after laparoscopic hysterectomy in this patient population. METHODS: All women undergoing laparoscopic hysterectomy by a member of the minimally invasive gynaecology team at The Ottawa Hospital, a tertiary academic referral centre, from May 2013 to February 2015 were eligible to participate regardless of patient comorbidities or surgical complexity. Strict perioperative protocols are presented. Factors associated with decreased success of same-day discharge and baseline and postoperative quality of life surveys were analyzed. RESULTS: Fifty-three patients were included. Overall success of same day discharge was 83.0%. Average age and BMI were 44.4 years and 29.8 kg/m2, respectively. Thirty-four patients (63.0%) had at least one prior abdominal surgery. Those who had their surgery as first case of the day had a 91.7% same-day discharge rate versus 64.7% if they did not (relative risk = 1.4 [range 1.0-2.0]; P = 0.02). Ninety-eight percent of participants would recommend same-day discharge. Clinically significant improvement in quality of life from baseline was observed in 5 of 8 of the Short Form 36 domains at 6 months. CONCLUSION: Same-day discharge from hospital is reasonable and well accepted for patients undergoing laparoscopic hysterectomy, even with complex surgical pathology. The implementation of a successful same-day discharge program would mean greater efficiency, economic benefits, and improved access to surgical care for women.

Axonal localization and mitochondrial association of precursor microRNA 338.

MicroRNAs (miRNAs) selectively localize to subcompartments of the neuron, such as dendrites, axons, and presynaptic terminals, where they regulate the local protein synthesis of their putative target genes. In addition to mature miRNAs, precursor miRNAs (pre-miRNAs) have also been shown to localize to somatodendritic and axonal compartments. miRNA-338 (miR-338) regulates the local expression of several nuclear-encoded mitochondrial mRNAs within axons of sympathetic neurons. Previous work has shown that precursor miR-338 (pre-miR-338) introduced into the axon can locally be processed into mature miR-338, where it can regulate local ATP synthesis. However, the mechanisms underlying the localization of pre-miRNAs to the axonal compartment remain unknown. In this study, we investigated the axonal localization of pre-miR-338. Using proteomic and biochemical approaches, we provide evidence for the localization of pre-miR-338 to distal neuronal compartments and identify several constituents of the pre-miR-338 ribonucleoprotein complex. Furthermore, we found that pre-miR-338 is associated with the mitochondria in axons of superior cervical ganglion (SCG) neurons. The maintenance of mitochondrial function within axons requires the precise spatiotemporal synthesis of nuclear-encoded mRNAs, some of which are regulated by miR-338. Therefore, the association of pre-miR-338 with axonal mitochondria could serve as a reservoir of mature, biologically active miRNAs, which could coordinate the intra-axonal expression of multiple nuclear-encoded mitochondrial mRNAs.

Increasing Minimally Invasive Hysterectomy: A Canadian Academic Health Centre Experience.

OBJECTIVE: An institution wide strategic plan was established to improve minimally invasive surgery (MIS) across all surgical divisions at The Ottawa Hospital (TOH). The primary objective of this study is to determine the change in MIS hysterectomy rate between 2005 and 2012 at this centre. Secondary objectives include determining the impact on overall length of stay (LOS) in hospital, complications, return to hospital, operating room time, and cost. METHODS: We performed a retrospective analysis of all hysterectomies for benign disease performed at TOH between 2005 and 2012. Cases were excluded if they were related to pregnancy or classified as "partial hysterectomy." The outcomes and cost of the approaches were compared. RESULTS: A total of 4337 hysterectomy cases were reviewed. The MIS hysterectomy rate increased from 40.1% in 2005 to 74.2% in 2012. There was a decrease in mean LOS from 2.5 to 1.6 days. This translated to a saving of 1898 inpatient bed days. Compared with laparotomy, laparoscopic hysterectomy was associated with a reduced risk of transfusion and a reduced risk of ileus, and vaginal hysterectomy was associated with an increased risk of postoperative abscess. There was no difference in rates of returning to hospital or other complications between women undergoing abdominal hysterectomy and women undergoing MIS hysterectomy (which included both laparoscopic and vaginal approaches). The mean (SD) cost per approach was $7241 ($1985), $4532 ($1718), and $5637 ($1579) for abdominal hysterectomy, vaginal hysterectomy, and laparoscopic hysterectomy, respectively. CONCLUSION: The initiatives implemented at TOH in 2007 resulted in a significant increase in the MIS hysterectomy rate, a decrease in mean LOS, and substantial theoretical cost savings for the hospital.

Oocyte cryopreservation and reciprocal in vitro fertilization in a transgender man on long term testosterone gender-affirming hormone therapy: a case report.

Objective: To report a successful case of oocyte cryopreservation and subsequent in vitro fertilization (IVF) in a transgender male receiving continued testosterone gender-affirming hormone therapy, followed by reciprocal embryo transfer (ET). Design: A case report of a rare case of fertility preservation in a transgender man with concomitant use of testosterone therapy for 4 years before and during ovarian stimulation. Setting: Private fertility clinic with university affiliation. Patients: A 26-year-old transgender man undergoing oocyte cryopreservation before gender-affirming surgery. Interventions: Fertility preservation using oocyte cryopreservation and IVF with reciprocal fresh ET into a cisfemale partner. Main Outcome Measures: Successful oocyte cryopreservation, oocyte thawing, and reciprocal IVF cycle. Results: Oocyte cryopreservation of 29 mature oocytes. Sixteen mature oocytes survived the thaw, and 12 were fertilized with intracytoplasmic sperm injection. A fresh ET of an advanced blastocyst resulted in a clinical pregnancy and live birth. Conclusions: Fertility preservation with oocyte cryopreservation or IVF with embryo cryopreservation is feasible for patients on continued long-term testosterone gender-affirming therapy. Future studies on egg quality and reproductive outcomes are required. Our case report demonstrates a promising outcome in this patient population.

Evaluation of Early Frozen Blastocyst Transfer in A True Natural Cycle Protocol in Comparison to A Hormone Replacement Protocol: A Single-Center Cohort Study.

OBJECTIVE: Timing of frozen embryo transfer (FET) within a purported window of implantation is of increasing interest, and there is a paucity of evidence surrounding the transfer of frozen embryos early within these frozen embryo transfer protocols. This study aimed to evaluate whether live birth rates were equivalent after FET of blastocysts 4 days after luteinizing hormone (LH) surge in a true natural cycle protocol, compared to a hormone replacement (HR) protocol. MATERIALS AND METHODS: Single-centre, retrospective cohort study involving patients undergoing autologous frozen blastocyst transfer from January 1st, 2013, to December 31st, 2016. Cycles were grouped according to their protocol: true natural cycle (hormonal detection of LH surge with FET scheduled four days later) versus HR cycle (luteal phase gonadotropin-releasing hormone agonist suppression, oral or vaginal estradiol and intramuscular progesterone starting five days before FET). A total of 850 cycles were included, 501 true natural cycles and 349 HR cycles. The primary outcome was the live birth rate, secondary outcomes included clinical pregnancy rate and miscarriage. Logbinomial regression models were performed adjusting for a priori selected variables. RESULTS: Adjusted resulted in live birth rates of 38.7 and 40.4%, [adjusted risk ratio (aRR): 0.96, 95% confidence interval (CI): 0.76-1.22, P=0.729] in the natural cycle and HR groups, respectively. The secondary outcome analyses did not demonstrate any statistically significant difference in the rate of positive human chorionic gonadotropin (hCG), clinical intrauterine pregnancy rate, or miscarriage rate. CONCLUSION: The timing of the FET four days after LH surge in a true natural cycle protocol results in equivalent live birth rates compared to a HR protocol. Results of this study suggest that the window of implantation within the natural cycle may be less finite than currently believed and further prospective studies evaluating the timing of frozen embryo transfer are warranted.

Comparative Embryo Development Outcomes following Extending Embryo Culture to Day 6: A Retrospective Cohort Study.

BACKGROUND: Past studies have shown that culturing slow-growing embryos from day 5 to day 6 may increase vitrification yield. This study aims to evaluate if the proportion of embryos eligible for vitrification increases by growing embryos not vitrified by day 5 to day 6. MATERIALS AND METHODS: In this retrospective cohort study, a Canadian tertiary-care clinic-based cohort was identified between August 2019 and December 2020. In vitro fertilization (IVF) cycles involving autologous oocytes with at least one viable day 5 embryo were selected for inclusion. We compared embryo developmental outcomes of IVF cycles performed before and after an embryo cryopreservation policy change. Prior to March 2020, good-quality day 5 blastocysts of any stage were eligible for vitrification, and after that date, good-quality expanded blastocysts on either day 5 or day 6 were eligible. The primary outcome is the comparative proportion of embryos eligible for vitrification. The secondary outcome is to identify embryo, maternal and cycle factors that are predictive of day 6 vitrification. RESULTS: A total of 3,438 viable embryos across 679 consecutive IVF cycles were included in this study. After the policy change, we found similar mean proportions of blastocysts eligible for cryopreservation (46.9% per IVF cycle in group 2 vs. 44.4% in group 1, mean difference 0.025, 95% confidence interval -0.021 to 0.071, P=0.28). The mean number of cryopreserved embryos were significantly higher in group 2 (mean 2.2 vs. 1.7 embryos, P=0.007). Factors that predicated an embryo's progression to day 6 included: younger age of egg provider, presence of an early blastocyst on day 5, and cycles involving surgically-retrieved sperm. CONCLUSION: A cryopreservation policy change to include good-quality full and expanded day 6 blastocysts while avoiding to vitrify early blastocysts on day 5 yielded comparable proportions of embryos eligible for vitrification per IVF cycle.

A Practical Approach to Fertility Considerations in Endometriosis Surgery.

Endometriosis surgery requires thoughtful consideration and planning for those with infertility or those who wish to conceive in the future. Clinical history, examination, imaging, and fertility assessment can help plan, prepare and provide goal-directed surgical interventions when required. Further understanding of the benefits and limitations of surgery on future fertility outcomes is essential for those who provide care for patients with endometriosis. Endometriosis is a prevalent gynecologic condition, especially among patients with infertility. Studies demonstrate that, from a fertility perspective, surgery for endometriosis likely has a beneficial impact on the chance of spontaneous conception; however, selecting the appropriate surgical candidate can be challenging. To make a fully informed decision with regard to surgery, it is important to determine the patient's fertility goals and to conduct a thorough workup. Among patients with endometriosis-related infertility, first-line-assisted reproductive technology (ART) is generally preferred over surgery. Specific consideration in cases of minimal or mild endometriosis, ovarian endometrioma(s), and deep endometriosis (DE) are required for targeted counseling. Patients with symptoms significantly impacting their quality of life (QOL), or indications to proceed with surgery (ie, risk of malignancy, organ obstruction, or dysfunction) are best managed with surgical care by an experienced team. Surgery should be considered cautiously given the risks of damage to ovarian reserve, adhesions, and surgical complications. Risk of damage to ovarian reserve is a particularly important consideration among patients with endometrioma(s), with or without low ovarian reserve, and surgical complications are especially prevalent among patients undergoing surgery for bowel endometriosis. Goal-directed surgical treatment, as opposed to the traditional perspective of complete disease eradication, may be of particular importance among selected patients whereby fertility is a priority.

Reduced live birth rates after embryo transfer in patients with prior cesarean delivery: A retrospective cohort study.

OBJECTIVE: To evaluate whether live birth rates following first embryo transfer (ET) among patients after cesarean delivery are lower compared to patients with only prior vaginal delivery. STUDY DESIGN: Retrospective cohort study including patients with prior delivery who underwent first subsequent embryo transfer (fresh or frozen) between January 2013 and September 2019. The primary outcome was live birth rate among patients with at least one prior cesarean delivery compared to vaginal delivery only. Secondary outcomes included positive serum hCG, clinical intrauterine pregnancy and miscarriage rates. We performed a subgroup analysis with the cesarean delivery group based on labour status at the time of delivery. We fit a multivariable log-binomial regression model. RESULTS: Total of 962 patients met inclusion criteria: 351 in the cesarean delivery group and 611 in the vaginal delivery group. Live birth rate was significantly lower in the cesarean delivery group compared to vaginal delivery group at 30.0% vs 36.9% [aRR 0.81, 95% CI 0.67-0.98]. We also found lower positive hCG [aRR 0.82, 95% CI 0.72-0.94] and clinical pregnancy [aRR 0.85, 95% CI 0.73-0.99]. There was no significant difference in miscarriage rate. A subgroup analysis within the cesarean delivery group in active labour demonstrated significantly lower live birth rates compared to the vaginal delivery group [aRR 0.67, 95% CI 0.49-0.92]. CONCLUSIONS: Live birth rates following first ET were significantly lower after cesarean delivery compared to vaginal delivery. These findings may be largely attributable to a subgroup of patients with prior cesarean delivery in active labour who may be at particular risk of reduced live birth rates after ET.