Testicular sperm retrieval and intra cytoplasmic sperm injection provide favorable outcome in spinal cord injury patients, failing conservative reproductive treatment.

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVES: The objective of this study was to determine the in vitro fertilization (IVF) outcome after testicular sperm extraction (TESE) in a group of spinal cord injury (SCI) male patients not compatible with conservative fertility treatment. SETTING: University-affiliated medical center. METHODS: Thirty two SCI patients (C2 to L2) were referred to IVF after repeated trials of electroejaculation (EEJ) or penile vibratory stimulation (PVS), and full andrological evaluation. Testicular sperm aspiration (TESA) was the method of choice for sperm extraction. Open TESE was performed only after a negative TESA attempt. Clinical pregnancy and live birth rates were determined. RESULTS: A total of 106 testicular procedures were performed. Sperm was found in 95 cycles (89.6%). The average metaphase II (MII) oocyte number was 11.0±4.2, an average of 5.1±2.3 oocytes became normally fertilized after Intra Cytoplasmic Sperm Injection (ICSI) (fertilization rate 57.1%). On average, 2.7±1.2 embryos were replaced. The clinical pregnancy rate was 32/106 (30.2%) per cycle and 19/32 (59.3%) per couple. Live birth rate was 62.5% (20/32). CONCLUSIONS: TESA/E and IVF can provide excellent prognosis for SCI patients that cannot be treated by EEJ or PVS.

IVF outcome with cryopreserved testicular sperm.

The introduction of intracytoplasmic sperm injection and the use of spermatozoa extracted from the testicles have changed the option for conception for azoospermic patients. The purpose of the present study was to evaluate the IVF outcome after using cryopreserved testicular sperm samples in comparison with fresh ones. A total of 667 in vitro fertilisation cycles with fresh or cryopreserved testicular sperm obtained by an open biopsy and testicular needle aspiration were evaluated. Sperm motility was present in 70.9% of the cycles in Group-I, 77.8% cycles in Group-II and in 83.3% In Group-III (NS). The fertilisation rates were similar in the three study groups (50%, 48.6% and 54.8% respectively). The pregnancy rates were 26.7%, 22.2% and 16.3% respectively (NS). The delivery rate, however, was significantly lower in Group-III (4.1%) than in Group-I and -II (18.4% and 15.9%, respectively, P < 0.05). The IVF results after use of cryopreserved testicular sperm are comparable with those obtained with the fresh specimens. Lack of sperm motility before cryopreservation does not exclude favourable outcome and therefore testicular sperm freezing is feasible whenever there are enough sperm cells in the extracted testicular tissue.

Does controlled ovarian stimulation prior to chemotherapy increase primordial follicle loss and diminish ovarian reserve? An animal study.

BACKGROUND: Storage of embryos for fertility preservation before chemotherapy is widely practiced. For multiple oocyte collection, the ovaries are hyperstimulated with gonadotrophins that significantly alter ovarian physiology. The effects of ovarian stimulation prior to chemotherapy on future ovarian reserve were investigated in an animal model. METHODS: Cyclophosphamide (Cy) in doses of 0, 50 or 100 mg/kg was administered to 38 adult mice (control, unstimulated). A second group of 12 mice were superovulated with equine chorionic gonadotrophin (eCG, 10 IU on Day 0) before Cy administration; hCG (10 IU) was administered (Day 2) followed by 0, 50 or 100 mg/kg Cy (Day 4). In both groups ovaries were removed, serially sectioned (7-day post-Cy), primordial follicles were counted and differences between groups evaluated. RESULTS: Follicle number dropped from 469 +/- 24 (mean +/- SE) to 307 +/- 27 and 234 +/- 19 with 50 or 100 mg/kg Cy, respectively (P < 0.0001). In the eCG pretreated group, follicle count dropped from 480 +/- 31 to 345 +/- 16 and 211 +/- 26 when 50 or 100 mg/kg Cy were administered (P < 0.0001). There were no significant differences in follicle count between the pretreated eCG group and controls for each chemotherapy dose. CONCLUSIONS: This animal study indicates that ovarian stimulation before administration of Cy does not adversely affect ovarian reserve post-treatment. These results provide support for the safety of fertility preservation using ovarian stimulation and IVF-embryo cryopreservation procedures prior to chemotherapy.

Does age at orchidopexy impact on the results of testicular sperm extraction?

The aim of this study was to evaluate the affect of age at the time of orchidopexy on testicular sperm extraction (TESE) results among patients with a history of cryptorchidism and azoospermia. This retrospective study compared TESE results for couples undergoing IVF treatment, among two groups of patients. Group A included patients who underwent orchidopexy at age 10 and younger, and group B included patients who had the procedure above the age of 10. A total of 42 patients were included in the study. Forty patients had bilateral cryptorchidism and two had unilateral. The overall rate of sperm recovery was 59.5%. No differences were found in the sperm retrieval, fertilization, implantation, pregnancy, or live birth rates between the groups. The results suggest that age at orchidopexy, either at 10 years of age or younger or above 10 years of age, was not a predictive factor for successful TESE. Although bilateral cryptorchidism is usually considered a testicular secretory dysfunction, it was found that sperm retrieval attempts yielded spermatozoa in almost 60% of patients with azoospermia and a history of cryptorchidism.

IVF outcome in azoospermic cancer survivors.

OBJECTIVE: To assess clinical outcome among infertile couples treated by in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) using testicular sperm from azoospermic cancer survivors. STUDY DESIGN: This clinical retrospective study included infertile couples treated in a single tertiary referral center between 1996 and 2013. All male partners were cancer survivors who were diagnosed with azoospermia due to previous gonadotoxic treatments and referred to testicular sperm extraction (TESE). Retrieved sperm was used for IVF-ICSI among patients' spouses. Sperm retrieval rate and IVF-ICSI outcome were evaluated. RESULTS: Sperm was successfully retrieved in 12 out of 36 patients (33.3%) on initial TESE, with an overall sperm retrieval rate of 38.6% (17 of 44). Female patients were 29.8±5.1 years old. The average number of retrieved oocytes was 14.0±4.0 per cycle, with clinical pregnancy and live birth rates per successful TESE of 64% (11 of 17) and 58.8% (10 of 17), respectively. Age, serum FSH, testicular volume and time from chemotherapy to TESE were not significantly different between patients with successful TESE to those without. Patients suffering from seminomas had significantly higher sperm retrieval rate, as compared to patients who had Hodgkin's lymphoma (P=0.024). CONCLUSIONS: Post-chemotherapy azoospermia can be successfully treated with TESE and ICSI, and should be offered to azoospermic cancer survivors who did not cryopreserve sperm prior to their gonadotoxic treatments.

Pharmacokinetic profile of long-acting injectable risperidone at steady-state: comparison with oral administration.

The single dose pharmacokinetic profiles of long-acting injectable (LAI) risperidone and oral risperidone were extrapolated to steady-state. Plasma concentrations of the active moiety (unchanged risperidone + 9-hydroxy-risperidone) were measured by radioimmunoassay up to 72 h after a single oral 1 mg dose of risperidone in healthy volunteers (n = 12), and up to 84 days after a single intramuscular injection of 50 mg LAI risperidone in schizophrenic patients (n = 26). These data were projected to multiple dose regimens (4 mg/day for the oral formulation and 50 mg every 2 weeks for LAI formulation) using the software package WinNonlin, and average steady-state pharmacokinetic profiles were predicted. The most interesting results, obtained at steady-state, were a lower predicted peak plasma level (46 vs. 62 ng/ml) and a lower predicted degree of fluctuation between Cssmax and Cssmin (53 vs 145%) with LAI compared to oral administration, which is in line with actual steady state data on LAI risperidone. In conclusion, the pharmacokinetic profile of LAI risperidone administered every 2 weeks ensures a steady-state profile with concentrations falling in the interval observed with an equivalent oral dose but with lower and less fluctuations (i.e. 1/2 weeks vs 1/day).

Highest concentrations of prorenin and human chorionic gonadotropin in gestational sacs during early human pregnancy.

Prorenin is not only the biosynthetic precursor of renin; under certain circumstances in vitro prorenin exhibits reversible intrinsic renin activity and can form angiotensin from renin substrate with or without cleavage of the prosequence. Prorenin is the predominant form of renin synthesized by reproductive organs (ovary, chorion laeve of the placenta, uterine decidua). Its plasma concentrations increases 10-fold throughout pregnancy to 10-100 times that of renin; amniotic fluid prorenin concentration is even higher. No data are available of gestational fluid prorenin concentrations during early pregnancy. For the first 10 weeks there are two gestational cavities; the chorionic cavity then disappears and the smaller amniotic cavity becomes predominant. In this study we measured prorenin, renin, renin substrate and hCG in fluid aspirated from gestational sacs during the first trimester of gestation (predominantly chorionic) and during the second and third trimesters (amniotic). Seventeen patients had amniocentesis during the second or third trimester. Nine patients underwent selective abortion of multiple pregnancy at 7-12 weeks gestation. One patient underwent surgery at 5 5/7 weeks (26 days after conception) for a tubal pregnancy. Second and third trimester amniotic fluid prorenin maximum velocity (Vmax) (16 and 3 sacs, respectively) averaged 6,100 +/- 1,700 (SD) and 1,930 +/- 760 ng/mL.h, respectively (i.e. 1,700 and 540 ng/L.s). In gestational fluid collected before 8 weeks, prorenin Vmax was 10-fold higher, averaging 62,500 +/- 40,000 ng/mL.h (17,000 ng/L.s). The concentration was 140,000 ng/mL.h (39,000 ng/L.s) in the 5 5/7 week tubal pregnancy. In sharp contrast, at 10-12 weeks gestation (n = 3) prorenin Vmax was only 260 +/- 114 ng/mL.h (72 ng/L.s); human CG was also highest before 8 weeks (276,500 +/- 110,900 IU/L) and lowest at 10-12 weeks (1210 +/- 540 IU/L) with intermediate levels occurring later in pregnancy. This study shows that the highest biological levels of prorenin yet detected (close to 1 micrograms protein/mL) occur in gestational sacs in early pregnancy, consistent with a role for the renin-angiotensin system in embryonic development or placentation.

Estradiol- and progesterone-related increases in the renin-aldosterone system: studies during ovarian stimulation and early pregnancy.

To investigate the degree to which endogenous increases in estradiol (E2) and progesterone (P4) are associated with changes in the renin system, we studied eight patients undergoing ovarian stimulation for in vitro fertilization (FSH/human menopausal gonadotropin or clomiphene citrate for 5-11 days, followed by hCG). Three conceived and were followed for up to 62 days after hCG treatment. The others were followed until the end of the luteal phase. During the follicular phase, E2 increased 10-fold, PRA increased 2-fold, and absolute levels of E2 and P4 were positively correlated (r = 0.63; P < 0.05). After ovulation, which was induced by hCG, E2 fell by 50% (day 7), but there was a 50-fold increase in P4 and a further 5-fold increase in PRA. By day 14, E2 increased again in the women who conceived, to levels even higher than those in the follicular phase, and both P4 and PRA increased 2- to 3-fold between days 7 and 14. In contrast, E2, P4, and PRA returned toward baseline levels in the nonpregnant women. On day 21, E2, P4, and PRA remained very high in the pregnant women [E2, 2297 +/- 255 pg/mL (8430 pmol/L); P4, 103 +/- 22 pg/mL (328 pmol/L); PRA, 33 +/- 8 ng/mL.h (9.17 ng/L.s)]. During the luteal phase and early pregnancy, there was a positive relationship between PRA and P4 (r = 0.68; P < 0.05). There was also a positive relationship between PRA and E2 (r = 0.54; P < 0.05); compared to the follicular phase level, PRA was 4-fold higher in the luteal phase at any E2 level. Like renin, urinary aldosterone excretion (UA) increased 5-fold during the luteal phase (day 7) and by a further 3-fold between days 7 and 21 in the pregnant women, reaching very high levels [135 +/- 28 micrograms/day (375 nmol/day); n = 3]. PRA and UA positively correlated (r = 0.59; P < 0.08). Plasma angiotensinogen increased from 2146 +/- 283 ng angiotensin-I/mL (n = 8) to 3682 +/- 607 (n = 8) on day 7 and to 5353 +/- 799 (n = 3) on day 21. Urinary sodium excretion did not fall, and urinary potassium did not increase in coordination with the changes in renin and aldosterone. There was no hypokalemia. These results demonstrate marked increases in plasma renin and UA in coordination with increases in plasma E2 and P4 during ovarian stimulation and early pregnancy, and coordinated falls during luteolysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Pharmacokinetics of ketanserin in patients with cirrhosis.

The pharmacokinetics of ketanserin, a new serotonin S2 (5HT2) antagonist, were studied in 26 patients with cirrhosis. Patients were randomised to receive either a single oral dose of ketanserin 20mg (n = 14) or 40mg (n = 8) or an intravenous dose of ketanserin 5mg (n = 4). The plasma kinetics of ketanserin and its metabolite ketanserinol were determined over 48 hours, by high pressure liquid chromatography with a fluorometric detector. Pharmacokinetic parameters were calculated using noncompartmental analysis based on a statistical moment theory. The first-pass effect of ketanserin was markedly decreased after oral administration compared with results previously obtained in healthy subjects. The peak concentration was not higher in cirrhotic patients than in controls. This result could be due to an increase in the initial volume of distribution. The production of ketanserinol was reduced in cirrhotics. A decreased mean ketanserin elimination half-life (t1/2 = 12 +/- 4 and 10 +/- 3h vs 16 +/- 3 and 18 +/- 4h in healthy controls after oral ketanserin 40mg and intravenous ketanserin 5mg, respectively) contrasted with a substantial increase in t1/2 for ketanserinol (33 +/- 13 vs 19 +/- 4h). The volumes of distribution were also markedly reduced in patients with cirrhosis. These results suggest either a reduction in the oral dosage of ketanserin or an increase in the interval between doses in patients with cirrhosis.

Studies on sperm chromosomes in patients with severe male factor infertility undergoing assisted reproductive technology treatment.

The aim of the study was to determine the rate of chromosome abnormalities in testicular sperm after intracytoplasmic sperm injection due to severe male factor infertility. The study groups included patient with non-obstructive azoospermia (n=9), obstructive azoospermia (n=10), Klinefelter's syndrome (n=5) and normal controls (n=6, groups I-VI, respectively). The mean serum levels of FSH 17.5+/-8.2 (P<0.05), 3.5+/-2.6, 29.8+/-13.0 (P<0.05) and 3.1+/-0.4 mIU/ml, respectively. The rates of chromosome abnormalities were 19.6% (P<0.001), 8.2% (P<0.001), 6.3 and 1.6%, respectively. Chromosomes X and Y were significantly more involved in the aneuploidy than chromosome 18 in groups I and II. The present findings demonstrate a linkage between gonadal failure (high serum FSH levels) and sperm chromosome abnormalities. Our findings may explain the increased incidence of perinatal sex chromosome abnormalities found in severe male factor patients. Patients with non-mosaic Klinefelter's syndrome have comparable risk for sex chromosomes aneuploidy as the rest of the patients with azoospermia. Therefore, genetic screening during pregnancy or before embryo replacement should be carefully considered in severe male factor patient following in vitro fertilization (IVF).

Pharmacokinetics of itraconazole oral solution in allogeneic bone marrow transplant patients receiving total body irradiation.

A prospective study of the pharmacokinetics of itraconazole solution was performed in 11 patients who underwent allogeneic BMT (day of BMT = day 0) after a conditioning regimen including total body irradiation (TBI). Itraconazole solution (400 mg once a day) was given 7 days before BMT and continued up to the end of neutropenia unless another antifungal treatment was necessary. Blood samples were collected before itraconazole intake (Cmin) and 4 h later (Cmax) every other day for assays of itraconazole (ITRA) and its active metabolite hydroxy-itraconazole (OH-ITRA). The mean values of Cmin ITRA and OH-ITRA, respectively, were 287 +/- 109 ng/ml and 629 +/- 227 ng/ml at day -1 and 378 +/- 147 ng/ml and 725 +/- 242 ng/ml at day +1. The maximum Cmin values were observed at day +3. Six patients at day -1 (54%) and 8 at day +1 (72%) had satisfactory residual plasma concentrations of at least 250 ng/ml of unchanged ITRA. From day +1 to day +9, eight patients discontinued the itraconazole treatment, five of them had satisfactory plasma residual concentrations at this time. This work shows a good bioavailability of itraconazole oral solution during the early phase after allogeneic BMT, but more data are needed for the late phases.

Assessment of ovarian and uterine blood flow by transvaginal color Doppler in ovarian-stimulated women: correlation with the number of follicles and steroid hormone levels.

OBJECTIVE: To study the changes that occur in vascular resistance to flow in the utero-ovarian circulation and their correlation with the number of follicles and steroid hormone levels in patients undergoing ovarian stimulation with gonadotropin. DESIGN: In a prospective study, the impedance to flow in the intraovarian and uterine vessels was measured by means of transvaginal color flow Doppler imaging throughout the cycle. SETTING: University-based IVF program. PATIENTS: Eleven infertile patients undergoing ovarian stimulation with gonadotropin in preparation for IVF and ET. MAIN OUTCOME MEASURES: Intraovarian, uterine, and arcuate artery blood flow velocity waveforms, follicular growth, and serum E2 and P concentrations throughout the cycle. RESULTS: Pulsatility index (PI) of the intraovarian blood vessels and uterine artery decreased gradually during the follicular and luteal phase. The PI of the arcuate artery did not change significantly. The PI of the intraovarian blood vessels correlated with the number of follicles (> 15 mm; day of hCG). Serum E2 concentrations but not P demonstrated negative linear correlation with the PI of the intraovarian vessels and uterine artery. CONCLUSIONS: Induced cycles are associated with decreased impedance to blood flow in the utero-ovarian circulation. Intraovarian PI correlates negatively at each stage of the cycle with the eventual number of preovulatory follicles. Little or no changes are observed when the response to ovarian stimulation is poor.

Presence of sperm in the perivitelline space predicts fertilization rate after partial zona dissection.

OBJECTIVE: To examine the association of the number of spermatozoa present in the perivitelline space and sperm parameters with fertilization after partial zona dissection in male factor patients. DESIGN: Partial zona dissection was applied in 62 couples (84 cycles). A total of 524 oocytes underwent partial zona dissection (1/8 of the zona circumference) (partial zona dissection group) and 171 sibling oocytes were not manipulated (control group). A total of 326 manipulated oocytes were examined for the presence of spermatozoa in the perivitelline space. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Fifty-four (87%) couples had at least one complete failure of fertilization, and 8 (13%) couples had low fertilization rate (< 10%) in previous routine IVF attempts. MAIN OUTCOME MEASURES: Fertilization rate, cleavage rate, and the number of spermatozoa present in the perivitelline space after partial zona dissection. RESULTS: Monospermic and polyspermic fertilization rates were 22.3% and 6.7% in the partial zona dissection oocytes and 8.8% and 0.6% in the nonmanipulated oocytes, respectively. The cleavage rate was similar in the partial zona dissection and control group (69.2% and 66.6%, respectively). A total of 81 partial zona dissection embryos and 10 nonmanipulated embryos were transferred to the uterus of 34 women (39 cycles), resulting in four pregnancies. In 46% (18 of 39) of the patients who had both partial zona dissection and control oocytes, only the manipulated oocytes fertilized. In only 48.8% of partial zona dissection oocytes, spermatozoa were detected in the perivitelline space; in this group of oocytes the fertilization rate was 56.6%. Sperm count and morphology were not clearly correlated with the outcome of partial zona dissection. CONCLUSIONS: The partial zona dissection technique enhances fertilization of subfertile sperm. However, the low efficiency of the procedure, apart from being associated with a high polyspermic rate, is related to the failure of sperm to traverse the slit in the zona pellucida in approximately one half of the manipulated oocytes.

The natural history of multiple pregnancies after assisted reproduction: is spontaneous fetal demise a clinically significant phenomenon?

OBJECTIVE: To determine the rate of spontaneous fetal demise after heartbeats are demonstrated in multiple pregnancies conceived after IVF-ET. DESIGN: Retrospective case series. SETTING: University-based IVF-ET program. PATIENTS: Eighty-one patients in whom initial transvaginal ultrasound (US) study, performed at 5 to 6 weeks of gestation, identified more than one gestational sac. Total number of sacs was 191. INTERVENTION: Patients were followed by serial US examinations. MAIN OUTCOME MEASURE: Outcome of pregnancies. RESULTS: Twenty-four empty gestational sacs were identified in 21 patients, of whom 15 delivered, 2 miscarried, and 4 are currently ongoing beyond first trimester. Of the 167 initially viable embryos, 9 (5%) underwent spontaneous fetal demise. In 5 of these 9 pregnancies, initial US identified significant interfetal size variation. CONCLUSIONS: The rate of spontaneous fetal demise for a specific embryo in multiple gestation, after fetal heartbeats have been identified in early pregnancy, is 5%. This rate is similar to that seen in spontaneous conceptions. The chance of future fetal demise increases if first trimester interfetal size variation is significant.

Human sperm and hamster oocyte interaction: a model system to assess sperm entry into the oocyte after partial zona dissection.

A model system of hamster oocyte and human sperm interaction was used to assess sperm entry into the perivitelline space after partial zona dissection. The procedure of zona dissection was standardized by creating slits which included one fourth, one eighth, one eighth X 2, or one sixteenth of the zonal circumference. Manipulated eggs were allowed to interact with 1 X 10(6) sperm/mL for 3 hours. A single large or medium slit was equally effective in permitting sperm entry into 46% and 47% of the manipulated eggs, respectively. However, the longer slit doubled the average number of sperm detected in the perivitelline space. A second medium-sized slit increased the rate of sperm entry into the perivitelline space to 76%, but the incidence of damaged oocytes also increased. A small slit did not permit sperm entry into any of the manipulated oocytes. This heterologous system of gamete interaction provides a model to evaluate requirements for successful partial zona dissection or other related procedures for assisted fertilization in the human.

Zygote intrafallopian transfer may improve pregnancy rate in patients with repeated failure of implantation.

OBJECTIVE: To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregnancy rates (PRs) in patients with repeated failure of implantation in IVF-ET cycles. DESIGN: A case-control study. PATIENT(S): Criteria for patient selection included male factor or unexplained infertility, normal uterine cavity, and at least three failures of implantation in IVF-ET cycles in which at least three embryos were placed per transfer. Data on 70 patients who underwent 92 ZIFT cycles are presented. A control group consisted of patients with the same selection criteria who underwent an additional standard IVF-ET cycle during the same time period. INTERVENTION(S): Ovulation induction consisted of down-regulation with GnRH analogue followed by ovarian stimulation with FSH and hMG. Intracytoplasmic sperm injection was performed on the oocytes of all patients with male factor infertility. Zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval. MAIN OUTCOME MEASURE(S): Implantation rates and PRs in the ZIFT and control groups were compared. RESULT(S): The PRs and implantation rates were significantly higher in the ZIFT group than in the control group: 34.2% (24/70) and 8.7% (29/333) versus 17.1% (12/70) and 4.4% (13/289), respectively (P = 0.002 and P = 0.04). The cumulative conception rate for two ZIFT cycles was 59.3%. CONCLUSION(S): Zygote intrafallopian transfer should be considered a beneficial mode of treatment for patients with repeated failure of implantation in IVF and transcervical ET. More prospective randomized studies are needed to support this observation.

Sperm chromosome abnormalities in men with severe male factor infertility who are undergoing in vitro fertilization with intracytoplasmic sperm injection.

OBJECTIVE: To investigate the potential paternal contribution to the risk of fetal chromosomal anomalies after intracytoplasmic sperm injection (ICSI). DESIGN: Spermatozoa isolated from testicular tissue and ejaculated specimens of consenting patients undergoing testicular biopsy and ICSI were analyzed for chromosomes X, Y, and 18 by FISH. SETTING: Assisted reproductive technology program. PATIENT(S): Consenting patients undergoing testicular biopsy and ICSI, severe oligozoospermic patients, and normal fertile donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The rate of chromosome abnormalities in testicular sperm with regard to the type of azoospermia and ejaculated sperm compared to healthy men. RESULT(S): The mean serum levels of FSH in the groups with nonobstructive azoospermia (n = 9), obstructive azoospermia (n = 10), severe oligozoospermia (n = 9), and the normal donors (n = 6) were 17.5 +/- 8.2 (P<.05), 3.5 +/- 2.6, 14.6 +/- 3.5 (P<.05), and 3.1 +/- 0.4 IU/mL, respectively. The corresponding rates of sperm chromosome abnormalities among these groups were 19.6% (P<.001), 8.2% (P<.001), 13.0% (P<.001), and 1.6%, respectively. The corresponding rates of disomy among these groups were 7.8% (12 of 153 spermatozoa), 4.9% (18 of 367), 6.2% (109 of 1,751), and 1% (5 of 500 spermatozoa), respectively. Errors in chromosomes X and Y were significantly more common than in chromosome 18. CONCLUSION(S): The present findings demonstrate a linkage between gonadal failure (high serum FSH levels) and the occurrence of sperm chromosome aneuploidies. Our findings may explain the increased incidence of sex chromosome abnormalities found after IVF in the severe male factor patient population. Genetic screening during pregnancy or before embryo replacement should be considered carefully.

Pregnancy after subzonal insertion of cryopreserved spermatozoa from a patient with testicular seminoma.

The first pregnancy established after subzonal insertion of frozen-thawed sperm obtained from a patient with seminoma and severe oligoasthenospermia is reported. A total of 800,000 sperm with a poor progressive motility were recovered after thawing. Three to seven motile spermatozoa were injected into the perivitelline space of each of 10 oocytes, and seven sibling oocytes were coincubated and inseminated with 200,000 motile sperm/mL. Only 1 of the manipulated oocytes fertilized and was transferred to the uterus 65 hours after insemination at the eight-cell stage. A healthy boy weighing 3,600 g was delivered spontaneously at 38 weeks of pregnancy. This report gives hope to patients with testicular malignancy and severely impaired sperm function to maintain their reproductive potential through sperm banking and assisted fertilization techniques.

Transvaginal embryo aspiration--a safe method for selective reduction in multiple pregnancies.

OBJECTIVE: To evaluate pregnancy outcome after transvaginal selective embryo aspiration and to compare the results with those reported previously with other techniques for selective abortion. DESIGN: Retrospective case series. SETTING: University-based in vitro fertilization (IVF) program. PATIENTS: Nineteen women with multiple pregnancy who conceived after ovulation induction or IVF/gamete intrafallopian transfer. INTERVENTION: Transvaginal ultrasound-guided aspiration of the embryo(s) was performed at 7 to 8 weeks of gestation. MAIN OUTCOME MEASURES: Early and late complications related to the procedure, outcome of pregnancy, and birth weight. RESULTS: In 18 cases, the initial number of embryos (3 to 7) was reduced to two. In 1 case, the number of embryos was reduced from 4 to 3. None of the remaining fetuses vanished after the procedure. One patient delivered at 25 weeks and all other patients delivered healthy, viable infants (a pregnancy loss rate of 5.3%). CONCLUSIONS: Transvaginal embryo aspiration in early gestation appears to be a simple and relatively safe procedure for selective termination in patients with high-order multiple pregnancy. The cumulative loss rate of selective termination procedures previously reported by others is three times higher than the loss encountered in our series. This earlier procedure may be more acceptable to patients from emotional and religious points of view.

Induction of preovulatory luteinizing hormone surge and prevention of ovarian hyperstimulation syndrome by gonadotropin-releasing hormone agonist.

OBJECTIVE: To use gonadotropin-releasing hormone agonist (GnRH-a) instead of human chorionic gonadotropin (hCG) to induce oocyte maturation for in vitro fertilization (IVF). DESIGN: Pituitary and ovarian responses to GnRH-a and the outcome of IVF were studied prospectively. Data from patients injected with hCG were analyzed retrospectively. SETTING: Program of IVF at the Rambam (Governmental) Hospital, Haifa, Israel. PATIENTS AND INTERVENTIONS: One or two doses of buserelin acetate 250 to 500 micrograms were administered to six patients with moderate response (Estradiol [E2], 1,494 +/- 422 [+/- SD] pg/mL) and 8 patients with exaggerated response (E2, 7,673 +/- 3,028 pg/mL) to gonadotropin stimulation. Progesterone (P) and E2 were administered for luteal support. MAIN OUTCOME MEASURES: Gonadotropin-releasing hormone agonist effectively triggered luteinizing hormone (LH)/follicle-stimulating hormone (FSH) surge. Mature oocytes were recovered in all patients. Luteal E2 and P were lower than in patients injected with hCG. No signs of ovarian hyperstimulation syndrome were observed. RESULTS: Serum LH and FSH rose over 4 and 12 hours, respectively, and were significantly (P less than 0.05) elevated for 24 hours. Of all mature oocytes, 67% fertilized and 82% cleaved. Four pregnancies were obtained. CONCLUSIONS: A bolus of GnRH-a is able to trigger an adequate midcycle LH/FSH surge, resulting in oocyte maturation and pregnancy. Our preliminary results also suggest that it allows a more accurate control of ovarian steroid levels during the luteal phase and may prevent the clinical manifestation of ovarian hyperstimulation syndrome.