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In this case-control study of euthyroid first-cycle IVF patients ≥38 years old with singleton baby, miscarriage, biochemical pregnancy, and no pregnancy outcomes from 2005–2008, we assayed frozen serum for autoimmune thyroid disease (AITD) and thyroid function at cycle start, trigger, and 4 and 5 weeks' gestation. AITD prevalence in older infertile women was similar across clinical outcomes, and although AITD was associated with a higher baseline TSH, TSH remained within acceptable ranges, suggesting that T 4 supplementation may not affect maternal outcomes in older euthyroid AITD patients through 5 weeks gestation.

To explore the long- and short-term trends in LH-suppression protocol use and patient profile characteristics.Descriptive study, retrospective cohort.Large, university-based IVF center.Four thousand five hundred one fresh IVF cycles categorized by use of GnRH antagonist, luteal GnRH agonist, and follicular microdose GnRH agonist.None.Frequency of use of LH-suppression protocol, patient and cycle characteristics, and outcomes at 10-year (1996-2005), 5-year (2001-5), and 3-year intervals (2004-6).In both the40 andor=40 age groups, GnRH antagonist use increased from 2001 to 2005, while luteal GnRH agonist and microdose use decreased. The most recent luteal agonist patients were better responders and had higher implantation, clinical pregnancy, and delivery rates. Antagonist patients in the40 andor=40 age groups had a better response in 2005 than in 2001 with higher clinical pregnancy rates. Microdose patients responded worse in 2005 than in 2001, although pregnancy rates did not change significantly. Such trends were echoed from 2004 to 2006.The target population for GnRH antagonist has broadened to include younger, normal responders in addition to the traditional poor responder. Luteal agonist and microdose protocols are chosen less frequently and remain targeted toward good and poor responders, respectively.

Although several early IVF successes were achieved after transferring fully formed blastocysts, the majority of embryos replaced worldwide over the past 30 years have been at the cleavage stage. The programme at this study centre has previously found that delaying an embryo transfer to day 5 can reduce the chance for a high-order multiple gestation without compromising the pregnancy rate because fewer embryos can be replaced. To evaluate the impact of transfer day and embryonic stage at cryopreservation on cycle outcome, 6069 fresh and 706 frozen transfers from 2000-2006 performed at this study centre were retrospectively analysed. Approximately half of the fresh transfers were performed on day 3, with a shift to day-5 transfer over the study period with no change in cryopreservation incidence. Implantation, clinical pregnancy and live birth rates were significantly higher following day-5 transfer. When frozen-thawed embryos (2-cell to day-6 blastocysts) were transferred, acceptable pregnancy and live birth rates were achieved at all stages but thawed embryos transferred as day-5 blastocysts generated consistently higher clinical pregnancy and live birth rates. Transfer of embryos frozen on day 6 had the highest miscarriage and lowest live birth rates. Barring government regulation, an IVF programme's day for cryopreservation generally depends on its management of and success with fresh embryo transfer.

To reevaluate clinical management of isolated teratozoospermia, in couples initiating IVF.Retrospective analysis of fertility indices in 535 cycles.A large, university-based fertility center.Consecutive couples (n = 495) who had a semen analysis using Kruger/Tyberberg strict criteria at our center within 12 months before undergoing their first and/or second IVF cycle in 2002-2004 with2 million postwash, motile sperm on the day of egg retrieval.Eggs were fertilized either by conventional IVF or ICSI. Semen analysis and gamete/embryo manipulation was standardized in all cases.Fertilization, fertilization failure, pregnancy, and live birth rates.There was no statistical difference in fertilization, fertilization failure, pregnancy, and live birth rates in the first or second IVF cycle when comparing couples with isolated teratozoospermia (5% normal morphology) to those with a normal semen analysis. Furthermore, no improvement in these outcomes was noted when ICSI was used to treat these teratozoospermic couples.Because isolated teratozoospermia generally does not impact on the major indices of IVF, these patients need not be subjected to the unnecessary cost and potential risks of ICSI. Future studies, however, should focus on different sperm morphologic and biochemical parameters to determine if they are important for clinical management in IVF.

To assess whether the use of extended embryo culture can reduce the incidence of high-order multiple gestations, a retrospective analysis of 7,418 fresh ETs performed in a university-based IVF clinic from 1997-2003 was conducted, comparing program results before and after institution of a protocol to select patients for extended culture of in vitro fertilized embryos. The incidence of triplet pregnancies was significantly reduced in patients at highest risk for high-order multiple gestations, i.e., those at

To assess the rates of select obstetric outcomes in oocyte donation (OD) recipients aged35 years andor =40 years and compare them to similarly aged IVF patients.Retrospective anonymous questionnaire study.University-based IVF center.Live-birth outcome was experienced by 199 OD recipients and 488 IVF patients35 oror =40 years.The OD or IVF cycles.Response rate, pregnancy outcome, and complications.Response rate was 60%. The OD recipients had significantly higher rates of pregnancy-induced hypertension (PIH) than their IVF counterparts. The OD35 years had the highest rate (42%), followed by ODor =40 years (26%), IVFor =40 years (14%), and IVF patients35 years (12%). In twin pregnancies, the rates of PIH remained higher in the OD groups: OD35 years (56%), ODor =40 years (36%), IVFor =40 years (25%), and IVF35 years (22%). Twin pregnancy rate was lowest in IVF patientsor =40 years (19%) and a lower preterm delivery rate (16%) reflected this difference. The cesarean section rates were 50% for singleton and 78% for twin deliveries in the OD patients35 year; in OD patientsor =40 years, the rates were 75% and 84%, respectively.The OD recipients are at higher risk for untoward obstetric outcomes than their IVF counterparts. Young OD recipients reported the highest rate of PIH, warranting further investigation into an association between early loss of ovarian function and PIH.

Cell allocation and subsequent lineage commitment in the human embryo may be established as early as in the unfertilized oocyte. This phenomenon might be the result of subtle differences of gene expression and protein distribution. To assess whether gene expression profiling by reverse transcription–polymerase chain reaction could be a suitable tool for the detection of cell allocation and lineage commitment, the expression pattern of the putative inner cell mass marker gene Oct-4 and the trophectodermal marker genes β-HCG and β-LH were correlated in individual blastomeres of preimplantation human embryos. In 2- to 5-cell stage embryos, expression of β-HCG and Oct-4 mRNA was negatively correlated in all blastomeres with statistical significance, suggesting that cell allocation can be assessed by those markers at early stages. In 7- to 10-cell stage embryos, expression of β-LH and Oct-4 mRNA was negatively correlated in some blastomeres without statistical significance, suggesting that more experiments are necessary to decide if lineage commitment can be assessed in some cells by those markers at later stages.

In human embryos, blastomeres differentiate into trophectoderm (TE) cells and inner cell mass (ICM) cells of blastocysts. Although morphologically indistinguishable, blastomeres at early cleavage stages are likely to undergo changes on a molecular level that make them destined to become ICM or TE cells. While the transcription factor Oct-4 might serve as a marker for totipotent ICM cells, human chorionic gonadotrophin might be used as the equivalent for TE cells. This study reports a reverse transcription-polymerase chain reaction procedure to assess human beta-HCG mRNA concentrations as well as ploidy in individual blastomeres from normally and abnormally fertilized human embryos. beta-HCG mRNA was detected in both euploid and aneuploid cells and in oocytes. Surprisingly, beta-LH mRNA was also detected in some euploid blastomeres. In regard to preimplantation genetic diagnosis, assessment of expression levels of beta-HCG and Oct-4 mRNA in individual biopsied cells might serve as a tool to identify embryogenic blastomeres in combination with testing for chromosome and single gene abnormalities.

Objective: To investigate the effects of two virucidal compounds, MAP30 (Momordica anti–human immunodeficiency virus [HIV] protein; molecular weight, 30 kd) and GAP31 (Gelonium anti-HIV protein; molecular weight, 31 kd), obtained from Momordica charantia and Gelonium multiflorum , respectively, on the motility and vitality of human spermatocytes. Design: Prospective, controlled study. Setting: New York University School of Medicine. Patient(s): Ten healthy men undergoing evaluation for infertility provided 10 semen specimens. Intervention(s): Human sperm were treated with the anti-HIV agents, MAP30 and GAP31. Nonoxynol-9, a commonly used spermicide, and phosphate-buffered saline were used as the positive and negative controls, respectively. Main Outcome Measure(s): The motility and vitality of human spermatocytes treated with MAP30 and GAP31 at doses that inhibit HIV-1 and herpes simplex virus. Result(s): MAP30 and GAP31 did not inhibit the motility or vitality of human sperm cells over a dose range of 100–0.1 μg/mL, whereas nonoxynol-9 demonstrated spermicidal action on all 10 samples over the same dose range. Conclusion(s): The antiviral agents, MAP30 and GAP31, were not toxic to human sperm cells at the doses at which they inhibit HIV-1 and herpes simplex virus. They had no effect on the motility of spermatozoa, even at a dose of 1,000 times the maximum effective concentration. These results indicate that MAP30 and GAP31 may be useful as nonspermicidal protection against sexually transmitted diseases.

Objective: To assess the impact of ET difficulty on IVF outcome and to optimize the ET procedure. Design: Retrospective analysis of IVF outcome by ET catheter type and ET difficulty. Prospective treatment and follow-up of patients with a history of extremely difficult cervical passage. Setting: Large university-based IVF program. Patient(s): All patients Intervention(s): Surgical correction of cervical stenosis. Main Outcome Measure(s): Pregnancy and embryo implantation rates. Result(s): Only 0.6% of ETs were "extremely difficult." Pregnancy rates were not statistically significantly different among ETs graded easy, moderate, and difficult. In contrast, no pregnancies occurred in the rare "extremely difficult" ET group. Eight patients with a history of extremely difficult cervical passage underwent surgical correction of their cervical stenosis. Twelve postoperative IVF-ET in these women resulted in eight clinical pregnancies, six of which were multiple gestations. The embryo implantation rate of these cycles was 42.2%. Conclusion(s): Patients with a history of extremely difficult ET may benefit from hysteroscopic evaluation and possible modification of their cervical canal before a future IVF attempt.

Objective: To describe different techniques of testicular tissue culture and their effect on sperm motility, mainly in cases of totally immotile spermatozoa, and to compare the effect of in vitro culture with that of motility stimulants. Design: Prospective study. Setting: University teaching hospital. Patient(s): Ten patients undergoing testicular biopsy for diagnostic purposes or for intracytoplasmic sperm injection. Intervention(s): Dissected testicular biopsy samples and tissue blocks were cultured at 37°C for up to 96 hours. Immediately after dissection, immotile testicular spermatozoa were incubated for 30 minutes in pentoxifylline and 2-deoxyadenosine. Main Outcome Measure(s): Sperm motility and vitality. Result(s): Overall, dissected samples showed improved sperm motility, which peaked within 48 hours of culture. Unlike motility, vitality declined linearly, from 56.3% ± 19% at initial assessment to 18.8% ± 11% at 96 hours. Five samples had initially immotile spermatozoa, of which four acquired motility at 48 hours. In vitro culture showed results comparable with those of incubation with pentoxifylline and 2-deoxyadenosine. Culture of tissue blocks did not improve motility or vitality compared with dissected tissue. Conclusion(s): The motility of testicular spermatozoa was enhanced or initiated after in vitro culture. Testicular biopsy culture may be an alternative to the use of motility stimulants to obtain motile spermatozoa for intracytoplasmic sperm injection, particularly when oocytes are not immediately available.

Objective: To look for correlations between acridine orange (AO) staining and semen parameters before and after sperm separation procedures and to assess whether the AO test predicts fertilization or pregnancy outcomes after standard IVF and intracytoplasmic sperm injection. Design: Prospective study that simultaneously assesses sperm morphology and nuclear protein maturity on a cell-by-cell basis before and after preparative procedures. Setting: University teaching hospital. Patient(s): Men (n = 140) undergoing diagnostic semen analysis. Main Outcome Measure(s): Acridine orange fluorescence of sperm nuclei, semen parameters, IVF outcome. Result(s): In unprocessed samples, 90% of sperm with normal heads displayed green fluorescence (mature nuclear protein); significantly lower percentages of green fluorescence were observed in sperm with abnormal heads. The percentage of mature normal sperm in the specimen correlated with motility. Sperm maturity after swim-up or Percoll gradient was significantly improved for sperm with normal or abnormal heads. The percentage of mature normal sperm correlated with motility after either Percoll or swim-up. Neither the percentages of mature nuclei nor mature normal nuclei correlated with fertilization or pregnancy outcome. Conclusion(s): Nuclear protein maturation correlates with sperm motility and morphology. Because morphologically normal and motile sperm are more mature, separation procedures should generate a population of sperm with the highest fertilization capacity. Acridine orange staining, however, did not predict fertilization efficiency or pregnancy outcome in IVF cycles.

OBJECTIVE: Our purpose was to evaluate whether tamoxifen has estrogenic endometrial effects as defined by histologic study or alterations in steroid hormone receptor expression. STUDY DESIGN: Nineteen postmenopausal tamoxifen-treated breast cancer patients who also had endometrial sampling were identified from files in the Department of Obstetrics and Gynecology. To examine the subgroup of 15 polyps, age-matched, non–hormonally treated patients with polyps ( n = 8) or atrophic endometria ( n = 5) served as comparison groups. Proliferative ( n = 3) and secretory ( n = 5) endometria served as procedural controls. Immunohistochemical studies for steroid receptors (estrogen, progesterone) were performed. RESULTS: Glandular cell progesterone receptor was significantly increased and stromal cell estrogen receptor was significantly decreased in tamoxifen-treated versus atrophic endometria. Progesterone receptor staining was not significantly different in tamoxifen-treated versus control polyps, although staining was high in both groups. Stromal cell estrogen receptor staining was significantly reduced in tamoxifen-treated versus control polyps, although there were no histologic differences. Reduced stromal cell estrogen receptor and increased glandular cell progesterone receptor staining was found in all tamoxifen-treated endometria regardless of the diagnosis. CONCLUSION: The tamoxifen-associated changes in endometrial steroid receptors support an estrogenic effect that is independent of histologic diagnosis and duration of use. This may contribute to the pathogenesis of tamoxifen-associated polyps and carcinomas. (Am J Obstet Gynecol 1997;176:129-37.)

Objective To identify the incidence, risk factors, and obstetric/perinatal outcomes associated with monozygotic twins (MZTs) after IVF. Design Nested case-control. Setting University-based center. Patient(s) The IVF cycles eventuating in pregnancy from 2000–2009. Intervention(s) None. Main Outcome Measure(s) The MZT incidence, chorionicity/zygosity, pregnancy/neonatal outcome. Result(s) Of 6,223 gestations, 131 MZTs were diagnosed (2.1% incidence; 2.0% in autologous and 2.7% in donor IVF cycles), 10 were dichorionic, and 121 were monochorionic. Controlling for all risk factors, young oocyte age, extended culture (noncleavage embryos transferred on/after day 4), and year of IVF treatment cycle were significantly associated with MZT. When assessing factors associated with specific MZT placentation, day 3 assisted hatching correlated more with dichorionic MZT, whereas extended culture and advanced day 5 embryonic stage correlated with monochorionic MZT. Comparing monozygotic to dizygotic multigestation outcomes, MZT fared worse; however, once controlling for triplet gestation, only gestational age at delivery remained significantly compromised in the monozygotic group. Conclusion(s) After IVF the incidence of MZT is high, with young oocyte age, year of treatment, and extended culture (or embryo stage at transfer) conferring greatest risk. Regarding MZT type, assisted reproductive technology (ART) procedures may influence the timing of embryonic splitting (i.e., division in early embryonic development may be influenced by zona pellucida [ZP] manipulation whereas later splitting may occur during delayed implantation). Poor obstetric/perinatal outcome is significantly impacted by the presence of an "extra" fetus, as high-order multiple gestation concurrent with an MZT conveyed the worst prognosis.

Midodrine, a peripheral α-adrenergic agonist, was evaluated in 7 female and 2 male patients with familial dysautonomia (FD), a disorder characterized by decreased sympathetic innervation. Prior to and after three months of midodrine treatment, each patient's response to postural change was assessed by arteriosonde readings of blood pressure and heart rate, corrected QT-interval measurements, Doppler evaluation of renal blood flow and circulating atrial natriuretic peptide (ANP) levels. The initial midodrine dose (2.5 mg three times daily) was raised until subjective symptoms improved. Doses were reduced if patients felt jittery or developed erect hypertension (systolic > 180 mmHg or diastolic > 110 mmHg). Midodrine, at an average dose of 0.25 mg/kg per day, improved subjective symptoms in all patients. With treatment, magnitude of blood pressure responses was variable. Although mean erect blood pressure did not increase significantly for the aggregate, it did increase in six of nine patients. In addition, the QTc interval normalized and erect renal perfusion improved. Changes in supine mean blood pressure and supine circulating ANP correlated directly. We judge midodrine to be useful in management of orthostatic hypotension in patients with familial dysautonomia.