Joseph A. Politch

A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles

OBJECTIVEnTo compare the efficacy of Crinone 8% intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET.nnnDESIGNnRandomized, open-label study.nnnSETTINGnAcademic medical center.nnnPATIENT(S)nTwo hundred and one women undergoing IVF-ET.nnnINTERVENTION(S)nWomen were randomized to supplementation with Crinone 8% (90 mg once daily) or IM progesterone (50 mg once daily) beginning the day after oocyte retrieval.nnnMAIN OUTCOME MEASURE(S)nPregnancy, embryo implantation, and live birth rates.nnnRESULT(S)nThe women randomized to luteal phase supplementation with IM progesterone had significantly higher clinical pregnancy (48.5% vs. 30.4%; odds ratio [OR], 2.16; 95% confidence interval [CI], 1.21, 3.87), embryo implantation (24.1% vs. 17.5%; OR, 1.89; 95% CI, 1.08, 3.30), and live birth rates (39.4% vs. 24.5%; OR, 2.00; 95% CI, 1.10, 3.70) than women randomized to Crinone 8%.nnnCONCLUSION(S)nIn women undergoing IVF-ET, once-a-day progesterone supplementation with Crinone 8%, beginning the day after oocyte retrieval, resulted in significantly lower embryo implantation, clinical pregnancy, and live birth rates compared with women supplemented with IM progesterone.

Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men

Objective:Although HAART can suppress genital shedding and sexual transmission of HIV, men who have sex with men (MSM) have experienced a resurgent HIV epidemic in the HAART era. Many HIV-infected MSM continue to engage in unsafe sex, and sexually transmitted infections (STIs) or other factors may promote genital HIV shedding and transmission in this population despite HAART. In this study, we determined the prevalence of seminal HIV shedding in HIV-infected MSM on stable HAART, and its relationship with a number of clinical, behavioral and biological variables. Design:Sexually active HIV-infected men using HAART were recruited from an MSM health clinic to provide semen and blood samples. Methods:HIV levels were assessed in paired semen and blood samples by PCR. Clinical and behavioral data were obtained from medical records and questionnaires. Herpes simplex virus 2 (HSV-2) serostatus, seminal HSV-2 DNA, and markers of genital inflammation were measured using standard laboratory methods. Results:Overall, HIV-1 was detected in 18 of 101 (18%) blood and 30 of 101 (30%) semen samples. Of 83 men with undetectable HIV in blood plasma, 25% had HIV in semen with copy numbers ranging from 80 to 2560. Multivariate analysis identified STI/urethritis (Pu200a=u200a0.003), tumor necrosis factor &agr; (Pu200a=u200a0.0003), and unprotected insertive anal sex with an HIV-infected partner (Pu200a=u200a0.007) as independent predictors of seminal HIV detection. Conclusion:STIs and genital inflammation can partially override the suppressive effect of HAART on seminal HIV shedding in sexually active HIV-infected MSM. Low seminal HIV titers could potentially pose a transmission risk in MSM, who are highly susceptible to HIV infection.

Is leukocytospermia clinically relevant

OBJECTIVEnTo evaluate the relationship between seminal leukocytes and abnormal semen parameters in a large population of infertility patients.nnnDESIGNnProspective clinical study.nnnSETTINGnCenter for Reproductive Medicine at Brigham and Womens Hospital, Boston, Massachusetts.nnnPATIENT(S)nOne thousand seven hundred ten male partners in infertile couples attending the Center for Reproductive Medicine.nnnMAIN OUTCOME MEASURE(S)nSeminal leukocyte concentrations, sperm count, motility and morphology, and the prevalence of samples with < 10 x 10(6) motile sperm per ejaculate (a parameter defined by IVF as the most clinically significant predictor of male infertility).nnnRESULT(S)nThere was a strong relationship between increasing leukocyte concentrations in semen and abnormal semen parameters. Statistically significant differences in sperm concentrations and morphology were observed at leukocytospermia thresholds of 5 x 10(5) and 2 x 10(6) granulocytes/mL, respectively. The percentage of suboptimal semen specimens as defined by IVF criteria (< 10(7) total motile sperm per ejaculate) significantly increased with increasing seminal granulocyte concentrations. A twofold increased prevalence in such suboptimal semen specimens was observed at the leukocytospermia threshold of 2 x 10(6) granulocytes/mL.nnnCONCLUSION(S)nThere is a relationship between increasing seminal granulocyte concentrations and poor semen parameters. At seminal granulocyte concentrations > 2 x 10(6)/mL, semen parameter abnormalities were observed that were both statistically and clinically significant.

Antibiotic therapy and leukocytospermia: a prospective, randomized, controlled study*

OBJECTIVEnTo determine the efficacy of common antibiotic therapies for treatment of leukocytospermia of unknown etiology.nnnDESIGNnProspective, randomized, controlled clinical study.nnnSETTINGnFertility and Endocrinology Unit at Brigham and Womens Hospital, Boston, Massachusetts.nnnPATIENTSnOne thousand seven hundred ten male partners in infertile couples attending the Fertility and Endocrinology Unit.nnnINTERVENTIONSnConcentrations of seminal peroxidase-positive granulocytes were determined during all routine semen analyses performed over a 30-month period. Of 119 men found to have leukocytospermia (> 10(6) granulocytes/mL semen) on first visit, 54 agreed to be randomized into one of three groups, and 41 patients completed the study. Group I (n = 13) and their wives received a 14-day course of oral doxycycline, 100 mg twice per day. Group II (n = 11) and their wives received a 14-day course of oral trimethoprim 160 mg-sulfamethoxazole 800 mg twice per day. Group III (n = 17) and their wives received no therapy. Four weeks after randomization, repeat semen analyses and granulocyte quantitations were done.nnnRESULTSnNeither of the antibiotic regimens resulted in a significantly higher rate of resolution of leukocytospermia over that seen in the control group.nnnCONCLUSIONSnThere is a high rate of spontaneous resolution of leukocytospermia after one positive test. Antibiotics are no more beneficial than no therapy for treatment of this condition.

Comparison of methods to enumerate white blood cells in semen

Seminal WBC counts obtained by an mAb-based immunohistologic method correlated well with seminal granulocyte counts obtained with a simple peroxidase method (rho = +0.70; P < 0.0001). However, total WBC counts were significantly higher than granulocyte counts for most samples. With the immunohistologic method, 17 of 112 samples (15.2%) contained > 10(6) WBC/mL semen, whereas the peroxidase method resulted in only 10 samples (8.9%) with > 10(6) WBC/mL. When the threshold defining leukocytospermia was set at 1 x 10(6) positive cells/mL for both methods, the specificity of the peroxidase test compared with the immunohistology technique was 100% (10/10), but the sensitivity was only 58.8% (10/17). When the threshold for leukocytospermia in the peroxidase test was lowered to 5 x 10(5) positive cells/mL semen, the sensitivity relative to the immunohistology technique increased to 94.1% (16/17), and specificity remained 100% (16/16). Likewise, good interassay sensitivity and specificity values were obtained with thresholds of 10(6) WBC/mL for the peroxidase assay and 2 x 10(6) WBC/mL for the immunohistology assay. We conclude that either peroxidase or immunohistology assays can be used to screen for leukocytospermia, but that more research is needed to establish thresholds for pathological levels of WBC in semen using these two approaches. Total round cell counts are of no value for enumerating WBC in semen.

Sperm morphology and recurrent abortion.

In 98 men whose partners experienced three or more spontaneous abortions, there were no significant differences in ejaculate volume, concentration of sperm, the percentage of total abnormal sperm, or the percentage of individual sperm defects as compared with normal WHO standards and 17 men fathering successful pregnancies. These data indicate that neither abnormal sperm concentration nor abnormal sperm morphology are significantly associated with recurrent spontaneous abortion.

Extended in vitro maturation of immature oocytes from stimulated cycles: an analysis of fertilization potential, embryo development, and reproductive outcomes

PurposeTo investigate 24xa0h in vitro maturation (IVM) of cumulus-stripped immature oocytes from stimulated cycles.Methods263 oocytes identified as immature after cumulus stripping for ICSI were subjected to in vitro maturation (IVM). Fertilization rates and reproductive outcomes of matured oocytes were compared against 234 in vivo matured sibling oocytes (IVO-MII-Sib) from the same cycles (nu2009=u200941). Day 2 embryo development was compared against 116 embryos from ICSI cycles having no IVM (IVO-Ext controls).ResultsWhile fertilization rates were similar between IVM and IVO-MII-Sib oocytes (62.1% vs. 64.0%, pu2009=u20090.9909), day 2 embryo quality was reduced in the IVM group compared with IVO-Ext controls as evidenced by fewer embryos having 4 cells (28.3% vs. 54.3%, pu2009=u20090.0026), low fragmentation (30.0% vs. 65.2%, pu2009<u20090.0001) or perfectly symmetric blastomeres (28.6% vs. 46.9%, pu2009=u20090.0371). 0 of 17 IVM embryos with known fate implanted.ConclusionEfficacy of 24xa0h IVM for cumulus-stripped GV and MI oocytes for either clinical use or study of normal meiotic maturation is questionable.

Factors associated with the formation of triploid zygotes after intracytoplasmic sperm injection

OBJECTIVEnTo determine whether clinical or laboratory factors influence development of triploid (3PN) zygotes after ICSI.nnnDESIGNnRetrospective review.nnnSETTINGnThe assisted reproductive technology program of Brigham and Womens Hospital.nnnPATIENT(S)nPatients undergoing ICSI.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nCycles were divided into two groups: group A, cycles with one or more 3PN zygotes after ICSI, and group B, cycles with no 3PN zygotes. Age, amount of gonadotropin administered, peak estradiol levels, number of follicles, number of oocytes retrieved and injected, time between retrieval and injection, oocyte abnormalities, sperm type and motile count, percentage of diploid zygotes, and ongoing pregnancy rates were compared between groups.nnnRESULT(S)nCompared with patients in group B, those in group A received fewer ampoules of gonadotropins, had higher estradiol levels, and had more follicles on the day of hCG administration, oocytes, immature oocytes and oocytes injected and lower percentages of diploid zygotes. However, ongoing pregnancy rates did not differ between groups.nnnCONCLUSION(S)nPatients who produce 3PN zygotes after ICSI are high responders to ovarian stimulation. The appearance of such embryos is not associated with lower ongoing pregnancy rates and should not necessarily dictate alterations in ovarian stimulation protocols.

RESIDUAL ANDROGEN BINDING IN TESTICULAR FEMINIZATION (TFM)

Most mutants with genetic androgen-resistance possess some level of androgen binding which exhibits properties of receptors. The present studies aim to determine whether the androgen binding activities in mutants are, or are related to, receptors. This binding portion is termed residual androgen receptors. We have examined several androgen-resistance mutants with testicular feminization (TFM). Putative androgen receptors from mice, rats, and humans with TFM have been compared, and at least three different types of residual receptors have been observed. They are discussed in relation to possible receptor defects and to differences in the nature of androgen-resistance associated with each of them.

Conversion of high-response gonadotropin intrauterine insemination cycles to in vitro fertilization results in excellent ongoing pregnancy rates

OBJECTIVEnTo determine whether conversion of gonadotropin/IUI cycles at high risk of high-order multiple pregnancies to IVF yields a pregnancy rate high enough to warrant the added intervention.nnnDESIGNnCase-control study.nnnSETTINGnBrigham and Womens Hospital assisted reproductive technology program.nnnPATIENT(S)nSeventy-seven patients converted from gonadotropin/IUI to IVF, 77 consecutive age and attempt number-matched controls (sequential controls [SCs]), and 77 consecutive age-, attempt-, and E(2)-matched controls (E(2) controls [ECs]).nnnINTERVENTION(S)nGonadotropin/IUI cycles with exuberant responses were converted to IVF (cases) to avoid cycle cancellation and high-order multiple pregnancies.nnnMAIN OUTCOME MEASURE(S)nPregnancy rates, delivery rates, E(2) levels, follicle and oocyte number, and fertilization and implantation rates.nnnRESULT(S)nCompared with SCs and ECs, cases had more follicles (16.3 +/- 0.6 vs. 13.3 +/- 0.9 and 14.4 +/- 0.9) and higher E(2) at hCG administration (1,951 +/- 93 vs. 1,568 +/- 96 and 1,939 +/- 89 pg/mL). Delivery rates among the three groups (45.5% vs. 32.5% and 39.0%) did not differ significantly. Despite the transfer of fewer embryos in cases than in controls (2.5 +/- 0.1 vs. 3.1 +/- 0.1 and 2.9 +/- 0.1), three triplet pregnancies occurred in cases and three in controls.nnnCONCLUSION(S)nConversion of high responder gonadotropin/IUI patients to IVF is an effective alternative to cycle cancellation and offers a delivery rate as high or higher per cycle than that of planned IVF. Sample size limited the statistical power of the study.