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.

Novel fumarate hydratase mutation in a family with atypical uterine leiomyomas and hereditary leiomyomatosis and renal cell cancer.

OBJECTIVE: To describe a novel mutation in the fumarate hydratase (FH) gene in a family with atypical uterine leiomyomas. DESIGN: Case report and review of the literature. SETTING: Academic community hospital. PATIENT(S): Three sisters who presented as nulligravidas aged 27-30 years with large atypical uterine leiomyomas. INTERVENTION(S): Abdominal myomectomy, robotic myomectomy, hysterectomy, gene sequencing. MAIN OUTCOME MEASURE(S): Identification of a family with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome and a novel mutation in the FH gene. RESULT(S): Two of the three sisters tested positive for a novel FH mutation p.Leu99Glufsx6. The eldest sister was clinically diagnosed with HLRCC. The patients' father also carries the same mutation in the FH gene. The patients and their father are now undergoing yearly screening for renal cancer. CONCLUSION(S): Patients with HLRCC are at risk for developing renal cancer as well as losing their fertility via early hysterectomy. Physicians must be aware of this condition and refer at-risk individuals for genetic testing.

Uterine fibroids associated with infertility.

In recent years, there has been an increasing focus on the contributory role of uterine fibroids to infertility. The prevalence of these tumors increases with age, which becomes significant as more women are delaying childbearing. Therefore, fibroids and infertility frequently occur together. Treatment varies with fibroid location and size. The various methods of treatment include open myomectomy, laparoscopic or robot-assisted myomectomy, medical treatment, uterine artery embolization and magnetic resonance guided focused ultrasound surgery. While there is a general consensus on the treatment of submucosal fibroids, the management of intramural fibroids in the infertility patient remains controversial. This paper aims to review and summarize the current literature in regards to the approach to uterine fibroids in the infertile patient.

Randomized trial of harp therapy during in vitro fertilization-embryo transfer.

OBJECTIVE: This study evaluated whether harp therapy reduces levels of stress and improves clinical outcomes in patients undergoing embryo transfer. DESIGN: This prospective randomized trial enrolled 181 women undergoing embryo transfer, who were randomized to harp therapy during embryo transfer or standard treatment. Patients underwent standardized psychological testing and physiologic assessment of stress. SETTING: The study was conducted in a reproductive medicine practice. RESULTS: No statistically significant differences were found in the heart and respiratory rates, nor was there a significant difference in event-based anxiety at baseline. Harp therapy had a significantly larger decrease in state anxiety from pre- to post-embryo transfer. Clinical pregnancy was 53% versus 48% for the harp therapy and standard treatment groups, respectively. CONCLUSION: Harp therapy decreases state, or event-based, anxiety, significantly lowering state scores posttransfer and having a positive effect on acute levels of stress. There was an increased pregnancy rate, but larger sample sizes are needed to evaluate whether harp therapy has an effect on clinical outcomes.

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.

Role of coculture in human in vitro fertilization: a meta-analysis.

OBJECTIVE: To evaluate the role of coculture in human IVF. DESIGN: Meta-analysis. SETTING/PATIENT(S)/INTERVENTION(S): A literature search was performed using the Cochrane Menstrual Disorders and Subfertility Group Trials register, the Cochrane Central register of Controlled Trials on the Cochrane Library (2006), and MEDLINE (January 1966 to March 2006). MAIN OUTCOME MEASURE(S): Primary outcomes measured were implantation rates and pregnancy rates (clinical and ongoing). Secondary outcomes included evaluation of pre-embryo development based on average number of blastomeres per embryo. RESULT(S): A total of 17 prospective, randomized trials were identified. There was an overall statistically significant effect of coculture on the implantation rate, clinical pregnancy rate, and ongoing pregnancy rate. The cocultured embryos had greater numbers of blastomeres, although the data were heterogeneous. CONCLUSION(S): This is the first systematic, evidence-based review of randomized controlled trials to objectively determine the potential benefits of coculture in human IVF. The pooled data of human trials on coculture demonstrate a statistically significant improvement in blastomere number, implantation rates, and clinical and ongoing pregnancy rates.

Da Vinci-assisted abdominal cerclage.

OBJECTIVE: To report the first placement of an abdominal cervicoisthmic cerclage using the da Vinci robot. DESIGN: Case report. SETTING: Tertiary-care hospital. PATIENT(S): A 39-year-old female with a history of cervical insufficiency who required a cerclage and was not a candidate for transvaginal cerclage placement. INTERVENTION(S): Abdominal cervicoisthmic cerclage placement using the da Vinci robot. MAIN OUTCOME MEASURE(S): Ability to safely and successfully place an abdominal cerclage using the da Vinci robot. RESULT(S): Abdominal cerclage was successfully placed using the da Vinci robot. The patient had minimal blood loss and was discharged to home on the same day as surgery. CONCLUSION(S): Da Vinci robot-assisted abdominal cerclage placement is an innovative application of robotic surgery and may alter the standard of care for women who require this surgery.

Mouse ascites Golgi mucin expression abnormalities in natural cycle endometrial biopsies predict subsequent in vitro fertilization-embryo transfer (IVF-ET) failure in patients with previous IVF-ET failures.

We performed a double-blinded retrospective cohort study to determine whether endometrial expression of mouse ascites Golgi mucin in a natural, unmedicated cycle predicts subsequent IVF-ET outcome among women with prior IVF-ET failure and poor pre-embryo quality. We found a statistically significant decrease in clinical pregnancy rate among women with abnormal mouse ascites Golgi expression, a test which was found to have high positive predictive value for failed IVF-ET.

Accessory uterine appendage may be a new Müllerian malformation.

OBJECTIVE: To describe a case of an accessory uterine structure. DESIGN: Case report. SETTING: University affiliated, community-based hospital. PATIENT(S): A 35-year-old woman who presented for laparoscopic tubal sterilization. INTERVENTION(S): Laparoscopy, tubal sterilization, dye test, and excision of accessory uterine structure. MAIN OUTCOME MEASURE(S): Laparoscopic findings and resection of the anomaly. RESULT(S): Laparoscopy showed a hollow uterine appendage that communicated with the uterine cavity. This was completely excised. CONCLUSION(S): We report a rare case of a uterine anomaly that is inconsistent with the traditional classification system, and we offer a possible mechanism for its formation.

A randomized prospective trial comparing gonadotropin-releasing hormone (GnRH) antagonist/recombinant follicle-stimulating hormone (rFSH) versus GnRH-agonist/rFSH in women pretreated with oral contraceptives before in vitro fertilization.

OBJECTIVE: To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day. DESIGN: Prospective, randomized, multicenter study. SETTING: Private practice and university centers. PATIENT(S): Eighty patients undergoing IVF who met the appropriate inclusion criteria. INTERVENTION(S): Four study centers recruited 80 patients. The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days. The recombinant FSH regimen was begun on the following Friday. The GnRH-agonist group was treated with a long protocol; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm. When two follicles had reached 16 to 18 mm, hCG was administered. MAIN OUTCOME MEASURE(S): The primary outcome measures were the number of cumulus-oocyte complexes, day of the week for oocyte retrieval, and total dose and days of stimulation of recombinant FSH. Secondary efficacy variables included pregnancy and implantation rate; serum E(2) levels on stimulation day 1; serum E(2), P, and LH levels on the day of hCG administration; follicle size on day 6 and day of hCG administration; the total days of GnRH-analogue treatment; total days on OC; total days from end of OC to oocyte retrieval; and the cycle cancellation rate. RESULT(S): Patient outcomes were similar for the days of stimulation, total dose of gonadotropin used, two-pronuclei embryos, pregnancy (44.4% GnRH-antagonist vs. 45.0% GnRH-agonist, P=.86) and implantation rates (22.2% GnRH-antagonist vs. 26.4% GnRH-agonist, P=.71). Oral contraceptive cycle scheduling resulted in 78% and 90% of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist. A one day delay in OC discontinuation and recombinant FSH start would result in over 90% of oocyte retrievals occurring Monday through Friday in both groups. CONCLUSION(S): The OC pretreatment in recombinant FSH/GnRH-antagonist protocols provides a patient-friendly regimen and can be optimized for weekday retrievals. No difference was seen in number of 2PN embryos, cryopreserved embryos, embryos transferred, implantation and pregnancy rates between the two stimulation protocols.

Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss.

OBJECTIVE: To determine the fetal loss rate after documented fetal cardiac activity (7-week sonogram) and to evaluate the chromosomal makeup of these losses in IVF pregnancies. DESIGN: Retrospective analysis. SETTING: University-based IVF center. PATIENT(S): Two thousand fourteen consecutive IVF pregnancies with documented fetal cardiac activity. MAIN OUTCOME MEASURE(S): Miscarriage rates and karyotypes of pregnancy losses were analyzed. RESULT(S): The overall pregnancy loss rate after demonstrated fetal cardiac activity was 11.6% (233/2014). A highly significant increase in fetal loss with advancing maternal age was observed (<30 years = 5.3% vs. 31-34 years = 7.6% vs. 35-39 years = 12.8% vs. > or =40 years = 22.2%). Patients with a multiple gestation were more likely to deliver a live infant, compared with those with a singleton detected at a 7-week sonogram. Of the 233 losses in the study period, cytogenetic analyses were obtained for 74 (31.8%). Three specimens were nondiagnostic. Fifty-two patients had abnormal karyotypes (71.2% [52/71]). Eighty-two percent of the pregnancy losses in women aged > or =40 years were associated with chromosomally abnormal fetuses, compared with 65% of the losses in women aged <40 years (odds ratio, 3.35; 95% confidence interval, 0.96-11.97). CONCLUSION(S): Pregnancy loss after documentation of fetal cardiac activity is >10%. This loss is significantly increased with advancing maternal age. The major underlying cause of these losses seems to be chromosomal aneuploidy.

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.

Importance of the biopsy date in autologous endometrial cocultures for patients with multiple implantation failures.

OBJECTIVE: To analyze the effectiveness of autologous endometrial coculture by the cycle day of the endometrial biopsy. DESIGN: Retrospective study. SETTING: University-based IVF center. PATIENT(S): Two hundred eight patients with multiple IVF failures. INTERVENTION(S): Embryos were split and randomly allocated to growth on autologous endometrial coculture or conventional media. MAIN OUTCOME MEASURE(S): Embryo quality and pregnancy outcome. RESULT(S): The overall clinical pregnancy rate was 41.8%. Embryos grown on autologous endometrial coculture were of higher quality (more blastomeres and less fragmentation) than embryos grown with conventional media. Early luteal biopsies (<5 days after LH surge) for autologous endometrial coculture did not demonstrate an improvement in embryo quality as compared to the significant improvement demonstrated with later luteal endometrial biopsies (> or =5 days after LH surge). The date of the biopsy was predictive of pregnancy outcome when using autologous endometrial coculture (44.7% [> or =5 days after LH surge] vs. 18.8% [<5 days after LH surge], P=.012). CONCLUSION(S): We have demonstrated an improvement in embryo quality when using autologous endometrial coculture. The improvement in embryo quality and higher pregnancy rates were limited to biopsies > or =5 days after the LH surge. This suggests that mid/late luteal phase endometrium contains factors that enhanced embryo growth and subsequent implantation.