Arye Hurwitz

Endometrial NK Cells Are Special Immature Cells That Await Pregnancy

NK cells populate the human endometrium before pregnancy. Unlike decidual NK cells that populate the decidua during pregnancy, the NK cells present in the human endometrium, before pregnancy, have not been fully characterized. In this study, we provide a detailed analysis of the origin, phenotype, and function of endometrial NK cells (eNK). We show that eNK cells have a unique receptor repertoire. In particular, they are negative for NKp30 and chemokine receptor expression, which distinguishes them from any other NK subset described so far. We further show that eNK cells lack NK-specific functional phenotype and activity such as cytokine secretion and cytotoxicity, before IL-15 stimulation. Following such stimulation, endometrial NK cells acquire phenotype and function that are similar to those of decidual NK cells. We therefore suggest that eNK cells are inactive cells (before IL-15 activation and in relation to the known NK activity) that are present in the endometrium before conception, waiting for pregnancy.

Observer variability in the diagnosis and management of the hysterosalpingogram

OBJECTIVEnTo determine the reproducibility of hysterosalpingogram (HSG) interpretation and clinical management recommendations among trained observers.nnnDESIGNnFifty HSG films were distributed to five fertility practitioners with a mean of 20 years clinical experience. Each observer evaluated components of uterine and tubal status and provided clinical recommendations for hysteroscopy and laparoscopy.nnnSETTINGnUniversity hospital-affiliated reproductive endocrine practice.nnnINTERVENTION(S)nNone MAIN OUTCOME MEASURE(s): The level of agreement among observers for each uterine and tubal category as determined by the kappa(kappa) statistic. Determinants of clinical recommendation for further diagnostic studies were assessed.nnnRESULT(S)nThe level of agreement between observers as determined by kappa ranged from 0.645 in the hydrosalpinx category, indicating fair reliability, to 0.111 for pelvic adhesions, indicating poor reliability. The composite kappa for uterine status was 0.345 whereas the composite kappa for tubal status was 0.430. Agreement among observers concerning management showed marginal reproducibility with a kappa of 0.261. Overall, more than one abnormality of either the cavity or the fallopian tubes led to a diagnostic recommendation for further workup in > or = 90% of cases.nnnCONCLUSION(S)nIn a group of five experienced clinicians, there was considerable variability in the interpretation as well as the clinical management of the HSG. Physicians caring for infertile couples should be aware of this discrepancy and should, if possible, review carefully both the original films as well as the report of the attending radiologist in formulating their diagnostic evaluation and management plan.

Reproductive outcome of fresh or frozen–thawed embryo transfer is similar in high-risk patients for ovarian hyperstimulation syndrome using GnRH agonist for final oocyte maturation and intensive luteal support

BACKGROUNDnTriggering ovulation by GnRH agonist (GnRHa) in GnRH antagonist IVF protocols coupled with adequate luteal phase support has recently been suggested as a means to prevent ovarian hyperstimulation syndrome (OHSS). Our objective was to examine the outcome of fresh embryo transfer (f-ET) after triggering ovulation by GnRHa and providing intensive luteal phase supplementation, compared with that of the next first frozen-thawed embryo transfer (ft-ET) after cycles with the same protocol and cryopreservation of all the embryos.nnnMETHODSnWe performed a cohort study at a university-based IVF clinic. The study population was patients at high risk for OHSS. A daily dose of 50 mg i.m. progesterone in oil and 6 mg of oral 17-β-estradiol initiated on oocyte retrieval day in the f-ET group (n= 70). In the ft-ET group (n= 40) the embryos were cryopreserved and transferred in the next cycle.nnnRESULTSnThe live birth rate per f-ET was 27.1 versus 20% in the ft-ET groups [P = 0.4; rate ratio = 1.36 (0.65-2.81)]. The implantation, pregnancy and spontaneous abortion rates were comparable in both groups. None of the patients developed OHSS.nnnCONCLUSIONSnIn this observational cohort study, we showed that triggering ovulation with GnRHa and intensive luteal phase support is a promising new modality to prevent OHSS without the cost of cycle cancellation, ET deferral and reduced clinical pregnancy rates. Confirmation of these findings by RCTs is now required.

The hormonal response of patients with polycystic ovarian disease to subcutaneous low frequency pulsatile administration of luteinizing hormone-releasing hormone.

Four patients with oligoamenorrhea manifesting hormonal and clinical features of polycystic ovarian disease (PCOD) were selected for treatment. All patients had high luteinizing hormone (LH) levels and a basal LH/follicle-stimulating hormone (FSH) ratio of greater than 3. Three of them had high androgen levels with normal adrenal cortical function. The four patients were treated for 12 cycles by pulsatile LH-releasing hormone (LH-RH) subcutaneously. Frequency of pulses varied between once in every 120 to once in every 400 minutes in consecutive cycles, in an attempt to reverse LH/FSH ratio. The dose of LH-RH varied between 20 and 40 micrograms/pulse. Treatment was monitored hormonally by the determinations of LH, FSH, 17 beta-estradiol, prolactin, progesterone, testosterone (T) (total and free), androstenedione (delta 4A), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) every 2 days. The most striking change was the lowering of the LH/FSH ratio to the normal range, due to LH decrease and FSH increase with a pulse frequency of 180 to 240 minutes. DHEA-S levels reversed to normal in two patients and were reduced in one patient. T and delta 4A levels returned to normal with elevation to normal of SHBG. These hormonal improvements did not result in ovulation as expected (2 of 12 cycles). It may be assumed that either subcutaneous administration is inadequate in PCOD patients or that the frequency of pulses needed to correct the hormonal disturbances in PCOD patients differs from that needed for ovum maturation and ovulation.

Sex ratio is remarkably constant

OBJECTIVEnTo study whether the sex of the offspring is related to increasing parental age, gravidity, and parity, hypothesizing an altered male-to-female sex ratio with the advancing parental age.nnnDESIGNnA large retrospective cohort study.nnnSETTINGnThe study analyzed birth records of Hadassah Hebrew University Medical Center in Jerusalem from June 2003 to December 2006.nnnPATIENT(S)n35,837 birth records were analyzed including 941 multifetal deliveries, excluding foreign inhabitants (n = 744), missing data for the main study outcome (n = 2) and parturients over 50 years to control for egg donation (n = 26).nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nMale-to-female sex ratio.nnnRESULT(S)nThe male-to-female sex ratio of all the newborns was 1.05. This ratio did not change significantly with either maternal or paternal age. Neither gravidity nor parity affected the male-to-female ratio. The only factor that affected the regression of sex ratio was the length of gestation.nnnCONCLUSION(S)nSex ratio at birth is remarkably constant. No association was found between parental age or birth order and neonatal sex ratio.

The value of repeat testicular sperm retrieval in azoospermic men

To determine the predictive value of a previous testicular biopsy to the chance of sperm retrieval in the next testicular sperm extraction (TESE) procedure, we retrospectively analyzed the outcome of past sperm collection procedures and histopathology diagnoses of patients with nonobstructive azoospermia. Repeated TESE ensured a high recovery rate (96%) when the first recovery procedure had been successful and when hypospermatogenesis was diagnosed (77%); when no spermatozoa were found on the first attempt, a repeat TESE procedure was successful in one-third of the patients.

The effect of insulin on progesterone production and cellular growth in long-term cultures of human granulosa lutein cells

The direct action of insulin on human granulosa lutein cells (GLCs) in long-term cultures obtained from in vitro fertilization (IVF) cycles was investigated. Progesterone (P) secretion by GLC increased progressively in both basal and human chorionic gonadotropin (hCG; 100 mIU/ml) stimulated conditions up to 4 days in culture, and plateaued thereafter. Insulin (0.0025 mU/ml to 2500 mU/ml) had no effect on either basal or hCG stimulation during the culture period. GLC in culture formed a monolayer and multiplied at a rate of approximately once every 3 days. Neither morphology nor cell division was affected by insulin in supraphysiologic levels (25 mU/ml). These results suggest that GLC obtained from preovulatory follicles in an IVF program are already stimulated maximally by in vivo exposure to high doses of human menopausal gonadotropin (hMG)/hCG administered to the women. Contrary to its stimulatory effect on early preovulatory granulosa cells, insulin dose not affect P production, cellular morphology, or growth rate of luteinized granulosa cells.

Severe Fetal Distress with Hydramnios due to Chorioangioma

Abstract. A case is described of antenatal detection of a placental mass by ultrasound in a patient with hydramnios due to chorioangioma and who had a sinusoidal‐like pattern and positive oxytocin challenge test (OCT). The importance of frequent fetal heart rate monitoring in cases of supected chorioangioma is emphasized.

Infertility counseling for Orthodox Jewish couples

OBJECTIVEnTo examine traditional Jewish concepts and practices of reproduction, and define problems that may arise in members of Orthodox Jewish society that follows the Halachah (the Jewish codes of conduct).nnnDESIGNnExpert opinion based on clinical experience.nnnSETTINGnAcademic-affiliated fertility clinic situated in an observant Jewish community.nnnPATIENT(S)nOrthodox and Ultraorthodox (Haredi) couples of the Jewish community.nnnINTERVENTIONS(S)nWe examined traditional Jewish concepts and practices of reproduction and defined problems that may arise in Jewish Orthodox society.nnnMAIN OUTCOME MEASURE(S)nNone.nnnRESULT(S)nThe concepts and practices of reproduction of Orthodox religious Jewish couples may lead to halachic subfertility and modification of the usual infertility workup. Treatments are limited to and determined largely by considerations related to religious doctrine.nnnCONCLUSION(S)nUnderstanding the religious, social, and cultural background of patients, particularly religious Orthodox women, enables appropriate fertility counseling and treatment.

Monozygotic multiple gestation after intracytoplasmic sperm injection and preimplantation genetic diagnosis.

OBJECTIVEnTo report a possible association between intracytoplasmic sperm injection (ICSI)-preimplantation genetic diagnosis (PGD) and monozygotic multiple gestation.nnnDESIGNnSmall case series.nnnSETTINGnIn vitro fertilization unit in an academic medical center.nnnPATIENT(S)nThree patients were treated with ICSI-PGD for sexing as well as selection against a known translocation.nnnINTERVENTION(S)nTransfer of day 4 embryos to the uterus.nnnMAIN OUTCOME MEASURE(S)nClinical pregnancy.nnnRESULT(S)nTwo pairs of monozygotic twins and a triplet pregnancy.nnnCONCLUSION(S)nRepeated manipulation of the zona pellucida as well as extended embryo culture during ICSI-PGD treatments may result in monozygotic twin and triplet pregnancies.