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Objective: To evaluate the presence of merocyanine 540 (M540) bodies and their impact on the measurement of apoptotic biomarkers in human spermatozoa., Design: Case-control, prospective study., Setting: Academic centers., Patient(s): Fertile and subfertile subjects., Intervention(s): Semen samples from subfertile and fertile men, 11 per group, were analyzed for basic semen parameters and early (annexin-V binding) and late (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) sperm apoptotic biomarkers by flow cytometry. Samples were also stained with M540 to assess the presence of M540 apoptotic bodies., Main Outcome Measure(s): Presence of M540 apoptotic bodies., Result(s): Groups differed significantly in the expression of early and late apoptosis biomarkers. The percentage of M540 bodies between groups was not different. The exclusion of M540 bodies from TUNEL results did not have a significant impact on measurement in either fertile or subfertile groups., Conclusion(s): This study confirmed the occurrence of M540 bodies in semen and that male factor infertility is associated with an increased expression of apoptosis biomarkers. Moreover, we demonstrated that the presence of M540 bodies did not affect the quantification of apoptotic biomarkers in either group., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the incidence of gestational diabetes mellitus (GDM) in Mexican women with a history of infertility and polycystic ovary syndrome (PCOS) compared with women without PCOS matched by age, pregestational body mass index (BMI), and parity., Design: Historic cohort study., Setting: Level three medical institution., Patient(s): Group 1 (n = 52), women with a history of infertility and PCOS, and group 2 (n = 52), women without PCOS. Inclusion criteria were singleton pregnancy with ≤ 13 weeks of gestation. Exclusion criteria were pregestational diabetes mellitus and/or concomitant diseases., Intervention(s): Diagnosis of GDM was based on a 3-hour, 100-g oral glucose tolerance test (GTT) performed during the second trimester., Main Outcome Measure(s): Incidence and relative risk (RR) for GDM., Result(s): The incidence of GDM was 26.9% and 9.6% for groups 1 and 2, respectively (RR = 2.8; 95% confidence interval 1.08-7.2). No other between-group differences were observed in the incidence of miscarriage, preterm birth, premature rupture of membranes, preeclampsia, stillbirth, fetal malformations, or small or large for gestational age newborns., Conclusion(s): Pregnant Mexican women with a history of infertility and PCOS are at increased risk for developing GDM. This risk should be considered beginning early in the second trimester for a timely intervention and to improve the maternal-fetal prognosis., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of age on the expression of apoptotic biomarkers in human spermatozoa., Design: Cross sectional, prospective study., Setting: Academic centers., Patient(s): Healthy volunteers with proven fertility, stratified by age (n = 25, range: 20-68 years)., Intervention(s): Examination of serum hormone levels and basic semen parameters, and assessment of early (plasma membrane translocation of phosphatidylserine) and late (DNA fragmentation) sperm apoptotic markers by flow cytometry (using Annexin-V binding and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)., Main Outcome Measure(s): Apoptosis markers., Result(s): Advancing male age was significantly and positively correlated with Annexin-V binding results. Although not significant, there was a clear trend for increased DNA fragmentation in the older groups. The age threshold for these observations appears to be 40 years. Advancing male age was positively correlated with FSH and sex hormone-binding globulin (SHBG) levels, and negatively correlated with sperm concentration., Conclusion(s): Advancing male age is associated with the expression of early apoptotic markers as evidenced by significantly increased plasma membrane translocation of phosphatidylserine, as well as with a more subtle proportion of sperm carrying DNA fragmentation. This study confirmed that male age is also associated with a decline in sperm concentration., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The objective of this review was to examine the role of the various spermatozoal components suspected of actively participating in early human development. The contributions of the fertilizing spermatozoon to the oocyte include, as a minimum, the delivery of the DNA/chromatin, a putative oocyte-activating factor (OAF), and a centriole. Recent data indicate that spermatozoa may also provide the zygote with a unique suite of paternal mRNAs; some transcripts might be crucial for early and late embryonic development and deficient delivery, or aberrant transcription might contribute to abnormal development and arrest. Clinical evidence from assisted reproduction suggests that failure to complete the fertilization process, syngamy, or early cleavage might be the result of an early paternal effect. It is speculated that an abnormal release of a putative OAF and/or dysfunctions of the centrosome and cytoskeletal apparatus may mediate these effects. On the other hand, a later paternal effect resulting in embryonic failure to achieve implantation, pregnancy loss, and/or developmental abnormalities resulting from "carried over" sublethal effects may be associated with sperm nuclear/chromatin defects, including the presence of aneuploidy, genetic anomalies, DNA damage, and possibly other causes. These findings highlight the need for continuous monitoring of clinical results.

Objective: To study the efficacy of the aromatase inhibitor letrozole as adjuvant to recombinant FSH (rFSH) in controlled ovarian hyperstimulation (COH)., Design: Prospective, randomized, and blinded clinical study., Setting: Academic tertiary institute., Patient(s): Forty-one patients with unexplained infertility undergoing intrauterine insemination (IUI) therapy were randomized to receive either letrozole or clomiphene citrate (CC) as adjuvants to rFSH., Intervention(s): From day 3 to 7 of the cycle 2.5 mg/d letrozole or 100 mg/d CC were administrated. All patients received 75 IU rFSH starting on day 7 of stimulation until the day of hCG administration. Ovulation was triggered with recombinant hCG (250 microg) when the leading follicle(s) reached 18 mm in diameter. A single IUI was performed 36 hours later. The luteal phase was supplemented with micronized progesterone vaginally., Main Outcome Measure(s): Ovarian stimulation response (E(2) levels and number of follicles) was our primary outcome., Result(s): There were no differences in demographic characteristics between groups. Although there was a significantly lower peak serum E(2) level in the group receiving letrozole + rFSH compared with CC + rFSH (914 +/- 187 vs. 1,207 +/- 309 pg/mL, respectively; P<.007), there were no differences in the number of mature (>16 mm) preovulatory follicles. A significantly higher endometrial thickness was observed at the time of hCG administration in patients that received letrozole (9.5 +/- 1.5 mm vs. 7.3 +/- 1.1 mm; P=.0001). The clinical pregnancy rate was similar between groups (23.8% vs. 20%, respectively)., Conclusion(s): The aromatase inhibitor letrozole appears to constitute a good alternative to CC in patients with unexplained infertility undergoing gonadotropin-stimulated COH cycles combined with IUI therapy.

Objective: To examine whether a relationship exists between loss of mitochondrial transmembrane potential and plasma membrane translocation of phosphatidylserine (PS) in subpopulations of human spermatozoa of men consulting for infertility., Setting: A tertiary institutional research center., Design: Prospective observational study., Patient(s): Twelve infertile men and five fertile controls were compared., Intervention(s): Sperm subpopulations were compared after density gradient separation., Main Outcome Measure(s): Mitochondrial membrane potential was measured with a cationic dye, translocation of PS was evaluated with Annexin-V binding, and motion parameters were assessed manually., Result(s): In both the study and control groups and compared with the high-motility fraction, the low-motility fraction had significantly lower sperm motility and normal morphology, and significantly higher percentage of cells with disrupted mitochondrial membrane potential and plasma membrane PS translocation. There was a positive and significant correlation in both subfertile and control groups between the percentages of Annexin-V+ live cells and cells with mitochondrial membrane potential disruption (r = 0.82 and r = 0.85, respectively)., Conclusion(s): The correlation of plasma membrane PS translocation and loss of mitochondrial membrane potential is suggestive of an early apoptosis phenotype, as is typically observed in somatic cells identified in sperm subpopulations with percentage of low-motile cells. We speculate that such changes might be used as diagnostic markers of sperm dysfunction(s) and that increased levels found in subfertile men might be indicators of reduced fertility potential.

Objective: To critically discuss the current protocols for the management of controlled ovarian hyperstimulation in assisted reproduction technology., Design: Review of the literature and presentation of our experience., Main Outcome Measure(s): Ovarian response (peak serum estrogen levels, number of oocytes retrieved, quality of oocytes and embryos) and pregnancy outcome (clinical, delivery, and multiple pregnancy rates)., Result(s): Controversies still exist regarding selection of gonadotropin preparation, choice of adjuvant therapy with GnRH analogues, and use of oral contraceptive pills. Patients identified as intermediate responders have an excellent outcome with adjuvant therapy with either a GnRH agonist (long protocol) or a GnRH antagonist, but tailoring of gonadotropin dose must be performed to achieve optimized results. High responders perform favorably with gentler gonadotropin stimulation that minimizes the occurrence of ovarian hyperstimulation syndrome. On the other hand, results in low responders remain suboptimal both in terms of ovarian response and oocyte/embryo quality in spite of a variety of stimulation regimens used., Conclusion(s): Ovarian stimulation is a critical step in in vitro fertilization therapy. A variety of controlled ovarian hyperstimulation regimens are available and efficacious, but individualization of management is essential and depends on assessment of the ovarian reserve. Identification of the etiologies of poor ovarian response constitutes a formidable challenge facing reproductive endocrinologists.