Loss of Nuclear/DNA Integrity in Mouse Epididymal Spermatozoa after Short-Term Exposure to Low Doses of Dibutyl Phthalate or Bisphenol AF and Its Mitigation by Oral Antioxidant Supplementation.

Routine exposure to chemicals omnipresent in the environment, particularly the so-called endocrine-disrupting chemicals (EDCs), has been associated with decreased sperm quality and increased anomalies in testis. The decline in semen quality and testicular abnormalities have been attributed to the disruption of endocrine signaling as well as oxidative stress. The present study set out to examine the effect of short-term exposure of two common EDCs widely used in the plastic industry: Dibutyl Phthalate (DBP) and Bisphenol AF (BPAF). Our research objective was to focus on the post-testicular compartment of the epididymis, where spermatozoa acquire their functional capacity and are stored. The data obtained indicated no significant effect for either chemicals on sperm viability, motility or acrosome integrity. Neither of the EDCs had a noticeable effect on the structures of the testis and epididymis. However, substantial impact on the integrity of the sperm nucleus and DNA structure was evidenced by a significant increase in nuclear decondensation and DNA base oxidation. The damage observed was postulated to arise from the pro-oxidant properties of the EDCs generating excess of reactive oxygen species (ROS) and triggering a state of oxidative stress. This hypothesis was confirmed when the observed damage was largely blocked by co-administering EDCs with an evidenced-based antioxidant formulation.

Rapid impact of COVID-19 infection on semen quality: a case report.

A unique opportunity to conduct a longitudinal analysis of semen quality in a male subject immediately before, during and after COVID-19 infection, has revealed new insights into the impact of this virus on male reproductive function. A moderate COVID infection that did not require hospitalization resulted in a state of azoospermia that persisted for 4 weeks. Given that the duration of spermatogenesis and epididymal sperm maturation in the human is 78 days, we calculate that a viral attack on the germ line was initiated at or before the patient was symptomatic and may have been signalled by a sudden reduction in sperm count and motility, several weeks earlier. Before the virus had been fully cleared, reinitiation of spermatogenesis occurred as evidenced by spermatozoa reappearing in the ejaculate exhibiting high levels of motility but significant levels of oxidative DNA damage as measured by a modified 8-OHdG assay protocol. These unique data indicate that even a moderate COVID-19 infection is capable of rapidly inducing a state of azoospermia that rapidly reverses as the infection wanes.

Multicentric, prospective observational data show sperm capacitation predicts male fertility, and cohort comparison reveals a high prevalence of impaired capacitation in men questioning their fertility.

RESEARCH QUESTIONS: Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics? DESIGN: In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men. RESULTS: New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25-26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P < 0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20-29%, 30-39%, 40-49%, 50-59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P < 0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men. CONCLUSIONS: Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.

Randomized Controlled Trial of Autologous Endometrial Coculture Versus Traditional in Vitro Fertilization.

OBJECTIVE: To determine if autologous endometrial cell coculture improves embryo development and clinical outcomes. STUDY DESIGN: Patients who met the inclusion criteria were randomized to either traditional in vitro fertilization (IVF) (control, n=73) or autologous endometrial cell coculture (AECC) (n=61). All patients underwent endometrial biopsy on cycle day 5­10 post luteinizing hormone surge. A total of 129 patients underwent embryo transfer (69 control, 60 AECC). Clinical outcomes as well as embryonic quality measures were then compared between the 2 groups. RESULTS: The mean age, day 3 follicle-stimulating hormone, number of oocytes collected, and clinical outcomes were similar between the 2 groups. Embryo development was overall similar, with the exception that embryonic grade was significantly better with AECC than with control: 1.5 (0.04) vs. 2.6 (0.03), p<0.0001. There was no difference in implantation, live birth or multiple gestation rates. CONCLUSION: This is one of the largest prospective randomized controlled trials of AECC versus traditional IVF. There was significant improvement in embryo morphology in the coculture group, although clinical outcomes were similar between the groups. Further studies are necessary to achieve enough power to fully delineate the effects of coculture on IVF outcome.

Prognosis for clinical pregnancy and birth after transferring embryos derived from a cohort of incompletely mature oocytes at retrieval time.

The purpose of this retrospective study was to establish a prognosis for implantation, pregnancy and live birth rates in stimulated IVF cycles after transferring embryos derived from: 1/ retrieved immature oocytes that matured overnight in vitro (late mature group: LM); 2/ retrieved immature oocytes that matured overnight in vitro and were added to the embryos derived from retrieved mature oocytes (mixed embryos group: MX); and 3/ retrieved mature oocytes (mature group: M). The obtained implantation, clinical pregnancy and live birth rates for the LM group were: 5.6%, 11.4%, 11.4%; for the MX group were: 4.2%, 14.6%, 11.6%; and for the M group were: 14.6%, 45.2% and 33.3%, respectively. These measurements were significantly lower p<0.05 for the LM and MX groups in comparison to the M group. The number of oocytes retrieved and the number of embryos transferred were the lowest (p<0.001-0.05) for the LM group. It is concluded, that the retrieved immature oocytes are able to mature during overnight culture in vitro, be fertilized and provide developmentally competent embryos with the prognosis of 11% for the successful delivery.

Hyaluronan binding assay (HBA) vs. sperm penetration assay (SPA): Can HBA replace the SPA test in male partner screening before in vitro fertilization?

OBJECTIVE: To determine if a less expensive, easier, and faster to perform HBA test is clinically equal to the more complicated, technically challenging and expensive SPA test as a reliable indicator of sperm fertilizing capacity. DESIGN: Prospective study. SETTING: Andrology laboratory within In Vitro Fertilization Program. PATIENT(S): Semen samples from 26 infertility couples were analyzed. Both, normal and male factor patients were included. INTERVENTION(S): Male partner screening with the HBA and the SPA tests. MAIN OUTCOME MEASURE(S): Relationship between HBA and SPA test results. RESULT(S): The data obtained in this study showed no statistically significant relationship between the HBA and SPA results. The mean HBA scores 76.3%, 61.3% and 76.8% were statistically not significantly different as compared to patients with negative (<5), grey zone (5-8) and for positive (>8) sperm capacitation index values. CONCLUSION(S): The HBA is not predictive of the results of the SPA. Therefore, HBA test does not reduce the need for and cannot replace the SPA test in male partner screening prior to infertility treatment.

Outcomes of day-1, day-3, and blastocyst cryopreserved embryo transfers.

The optimal developmental stage for cryopreserving embryos in IVF-ET remains controversial. Our study demonstrates that besides an improvement in postthaw survival rate for day-1 and blastocyst cryopreserved ET over day-3, all three groups attained statistically similar implantation, clinical pregnancy, multiple, twinning, and male gender rates.

Effect of macroscopic or microscopic blood and mucus on the success rates of embryo transfers.

OBJECTIVE: To assess the effect of microscopic and macroscopic contamination of embryo transfer (ET) catheters with blood or mucus on in vitro fertilization (IVF)-ET success rates. DESIGN: Retrospective cohort study. SETTING: Infertility practice in teaching community hospital. PATIENT(S): Four hundred seventy patients undergoing IVF-ET. INTERVENTION(S): Controlled ovarian hyperstimulation and IVF-ET. MAIN OUTCOME MEASURE(S): Implantation rate (IR) and clinical pregnancy rate (CPR). RESULT(S): The IR and CPR of IVF-ETs were comparable regardless of the presence (26.59% and 48.78%, respectively) or absence (23.49% and 44.44%, respectively) of any type of contamination. Even when analyzing specific contamination categories (i.e., macroscopic blood, microscopic blood on the outer catheter, microscopic blood on the inner catheter, blood anywhere without mucus, mucus only, or blood and mucus combined), there was no statistical significance in IR (range: 21.17% to 26.69%) or CPR (range: 32.69% to 49.5%). CONCLUSION(S): In general, IR and CPR appear to be unaffected by ET catheter contamination, whether it is macroscopic or microscopic presence of blood or mucus.

Profound hypothyroidism-induced acute menorrhagia resulting in life-threatening anemia.

BACKGROUND: Menorrhagia is a very common gynecologic entity with a broad differential diagnosis which includes both hypothyroidism and hyperthyroidism. CASE: We present the case of a 31-year-old patient with acute menorrhagia causing life-threatening anemia that resulted from profound hypothyroidism. Despite timely institution of thyroid replacement, the patient required emergent embolization of a uterine arteriovenous malformation after dilatation and curettage failed to control her bleeding. She was stabilized and discharged to home on the sixth hospital day. Three years later, she successfully conceived and delivered a healthy infant. CONCLUSION: Our case demonstrates the importance of thyroid evaluation in the patient who presents with menorrhagia. Timely management with medical treatment as well as conservative surgical or radiological interventions can facilitate resolution of symptoms and preserve the patient's fertility potential.

Patient experience with follitropin alfa prefilled pen versus previously used injectable gonadotropins for ovulation induction in oligoanovulatory women.

OBJECTIVE: To evaluate patient satisfaction with the follitropin alfa prefilled pen (Gonal-f RFF Pen), compared with previously used injectable gonadotropins (vial/ampoules and syringe), in women undergoing ovulation induction (OI). RESEARCH DESIGN AND METHODS: Women aged 18-40 years undergoing OI for oligoanovulatory infertility were enrolled from nine US fertility centers in this prospective, open-label clinical trial. Participants received recombinant follitropin alfa using a prefilled pen. Patient satisfaction was determined using a pre-treatment questionnaire to assess gonadotropin treatments undertaken within 6 months of study initiation and an in-treatment questionnaire to assess satisfaction with the prefilled pen. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients who preferred the prefilled pen compared to previous injectable gonadotropin therapies. Efficacy and safety were also assessed. RESULTS: Seventy-three subjects were screened for the study; 62 enrolled, were treated with the follitropin alfa pre-filled pen, and 61 completed the in-treatment questionnaire. Sixty-one of 61 patients who stated a preference preferred the prefilled pen to previous injectable gonadotropin therapies (61/61; 100%; 95% confidence interval: [94.1-100.0%]). One patient did not state a preference. Of these 61 patients, 54 (89%) found that the prefilled pen instructions were easy to understand compared to 17 of 59 (29%) who thought instructions for the conventional syringes were easy to understand. When preparing their dose, significantly fewer patients contacted their healthcare provider two or more times during the treatment cycle when receiving treatment with the prefilled pen (2/61, 3%) than during the first treatment cycle with prior gonadotropin treatment, 11/59 (19%, p = 0.007). The pen interfered slightly or not at all with patients' normal daily activities in 61 of 61 patients (100%) versus 50 of 59 patients (85%) who had this opinion regarding injections during their prior treatment cycles (p = 0.003). All 61 patients who stated a method of injection preference found the prefilled pen less stressful to use than syringes and would recommend the pen to another woman considering gonadotropin treatment. A total of 10/62 (16%) subjects reported 18 treatment-emergent adverse events (AEs). Two cases of ovarian hyperstimulation syndrome occurred post-treatment and one serious AE occurred (post-treatment ectopic pregnancy). Injection site reactions were generally mild to moderate, with mild itching (6 patients, 9.7%) and moderate redness in one patient. Fifteen patients reported mild redness (24.2%). Mild bruising (21.0%), mild pain (33.9%), and mild burning (32.3%) were also reported by patients. Seven patients (11.3%) had moderate pain. CONCLUSIONS: In this open-label, non-comparative study, patients undergoing OI preferred administering gonadotropins using the follitropin alfa prefilled pen compared to their prior use of vials/ampoules and a syringe. Patients using the prefilled pen found it less stressful, easier to use and more convenient than a conventional syringe and would recommend the pen to another woman considering gonadotropin treatment.

Recognition and prevention of gastric injury during gynecologic laparoscopy.

BACKGROUND: Laparoscopy has become an essential tool for the gynecologist. Its use has dramatically increased, in part, because of technological advances, but also because of well-documented advantages over laparotomy in particular scenarios. Immediate recognition of a complication is essential for reducing morbidity and potential mortality. We report an inadvertent gastric injury during a diagnostic laparoscopy. CASE: A 36-year-old woman sustained a gastric perforation during the insertion of an umbilical 5-mm trocar. After the injury was recognized, the patient underwent exploratory laparotomy, and primary repair of the defect was performed. The patient had an uneventful postoperative recovery. CONCLUSION: Gastric injury is a rare complication of gynecologic laparoscopy. Identification of risk factors, the use of a nasogastric or orogastric tube to relieve any gastric dilatation before initiation of the procedure, and proper surgical technique may minimize such injuries.

Subcutaneously administered Menopur, a new highly purified human menopausal gonadotropin, causes significantly fewer injection site reactions than Repronex in subjects undergoing in vitro fertilization.

BACKGROUND: The safety and tolerability of a new highly purified, urine-derived human menopausal gonadotropin (hMG) preparation [Menopur] was compared with a currently available hMG [Repronex] in women undergoing in vitro fertilization (IVF). METHODS: This was a randomized, open-label, parallel-group, multicenter study conducted in subjects undergoing IVF. Women (N = 125), 18-39 years of age, underwent pituitary down-regulation with leuprolide acetate beginning 7 days prior to onset of menses and continuing up to the day before hCG administration. Subjects were randomized to receive subcutaneous (SC) Menopur (n = 61) or Repronex SC (n = 64) for a maximum of 12 days. All adverse events (AEs) were recorded and subject self-assessments of injection site reactions were recorded in a daily diary. RESULTS: Significantly fewer subjects in the Menopur group reported injection site reactions (P < 0.001) compared to the Repronex group. Overall, there was no statistically significant difference in the incidence of AEs between the two treatment groups. CONCLUSION: Menopur SC offers a greater safety and tolerability profile compared to Repronex SC.

Comparison of pregnancy, implantation, and multiple gestation rates for day 3 versus day 5 embryo transfers.

PURPOSE: To compare pregnancy, implantation, and multiple gestation rates resulting from day 3 and day 5 embryo transfers after in vitro fertilization emphasizing a subset of patients who met criteria for day 5 transfer but elected to undergo day 3 transfer. METHOD: A retrospective analysis of day 3 and day 5 embryo transfers from January 2001 to June 2002 were evaluated in a community teaching hospital setting. A total of 331 patients < or = 40 years old were included. Using Student's t test, chi2 test, and Fisher's exact test, we compared the pregnancy, implantation, and multiple gestation rates. RESULTS: Pregnancy, implantation, and multiple gestation rates were not significantly different between the subgroup who met criteria for day 5 embryo transfer but elected day 3 transfer. There was no significant difference between similar parameters in the overall comparison of day 3 versus day 5 embryo transfers. CONCLUSIONS: Blastocyst transfers have similar multiple gestation rates, pregnancy rates, and implantation rates when compared to day 3 embryo transfers.

Successful pregnancy resulting from cryopreserved pronuclear and cleaved embryos thawed and cultured to blastocysts, refrozen and transferred. A case report.

BACKGROUND: Twice-frozen, thawed embryos may have utilization in vitro fertilization (IVF) cycles. CASE: A 37-year-old woman with endometriosis and infertility returned five years after a fresh IVF cycle. Seven cryopreserved embryos (2 pronuclear [pn] and cleaved) were thawed, and five developed to the blastocyst stage. One blastocyst was transferred, and the remaining four were recryopreserved. This transfer did not result in pregnancy. The remaining four blastocysts were thawed, and two were transferred resulting in a live, singleton delivery. CONCLUSION: Pregnancy can result from cryopreserved 2-pn and cleaved embryos cultured to blastocysts, refrozen and then transferred at the blastocyst stage.