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Evaluation of basal estradiol levels in assisted reproductive technology cycles.

OBJECTIVE: To determine if basal E(2) screening increases the diagnostic accuracy of basal FSH screening and to determine whether basal E(2) levels correlate with outcome in ART cycles. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENT(S): Two thousand six hundred thirty-four infertility patients. INTERVENTION(S): Cycle outcome was evaluated after grouping patients by basal E(2) levels beginning at <20 pg/mL and extending to >100 pg/mL at 10 pg/mL increments. MAIN OUTCOME MEASURE(S): Retrieved oocytes, pregnancy rate, and cancellation rate. RESULT(S): Cancellation rates were significantly increased in patients with basal E(2) levels of <20 pg/mL or >/=80 pg/mL. Basal E(2) levels neither predicted pregnancy outcome nor correlated with ovarian response in those patients not canceled. CONCLUSION(S): Patients with basal E(2) levels of <20 pg/mL or >/=80 pg/mL had an increased risk for cancellation. Basal E(2) was predictive of stimulation parameters in patients 40 years or older. For those patients who proceeded to retrieval, there were no differences in pregnancy or delivery rates relative to basal E(2) levels. This suggests that irrespective of basal E(2) levels patients who produce more than three maturing follicles in response to stimulation have adequate ovarian reserve as evidenced by their pregnancy rates.

Cohort Studies↗

Basal antral follicle number and mean ovarian diameter predict cycle cancellation and ovarian responsiveness in assisted reproductive technology cycles.

OBJECTIVE: To determine the predictive value and define threshold levels for basal antral follicle number and mean ovarian diameter in patients undergoing ART cycles. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS: Two hundred seventy-eight patients who had ovarian measurements performed on cycle day 3 before beginning treatment with gonadotropins. INTERVENTION: Pretreatment ovarian ultrasound measurements. MAIN OUTCOME MEASURE: Number of oocytes retrieved, hormone levels, and cycle outcomes. RESULTS: A direct linear correlation was observed between mean ovarian diameter and basal follicle number. Both measures demonstrated a positive linear correlation with recovered oocytes, basal E(2), and peak E(2). Both demonstrated a negative linear correlation with ampules of gonadotropins administered, days of stimulation, patient age, cycle day 3 FSH, and FSH:LH ratio. An antral follicle count of </=10 or a mean ovarian diameter of <20 mm was associated with an increased risk of cycle cancellation. CONCLUSIONS: Ovarian diameter and basal antral follicle number identify patients who may respond poorly to ART stimulation. These ovarian measures correlate well with ART screening and stimulation parameters. This knowledge allows physicians to evaluate and counsel patients immediately before an ART stimulation and to optimize stimulation protocols.

Female↗

Role of periovulatory luteinizing hormone concentrations during assisted reproductive technology cycles stimulated exclusively with recombinant follicle-stimulating hormone.

OBJECTIVE: To study the effect of endogenous luteinizing hormone (LH) concentration on fertilization, pregnancy, and early pregnancy loss rates. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university center. PATIENT(S): One hundred sixty-six normogonadotropic patients undergoing IVF. INTERVENTION(S): Luteal phase pituitary down-regulation and recombinant FSH (Gonal-F) were used for ovarian stimulation. The mean of 4-5 serum LH concentrations, from stimulation days 5-12, was computed for analysis. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and early pregnancy loss rates according to periovulatory levels of LH. RESULT(S): Data were analyzed by stratifying patients according to a mean periovulatory LH value of 3 mIU/mL. After controlling for confounding variables with logistic regression, results showed that the fertilization rate was significantly lower in patients with a periovulatory LH <3 mIU/mL versus > or = 3 mIU/mL (52% and 58%, respectively; P=.03). Pregnancy rates and spontaneous abortion rates were similar in both groups. There were seven biochemical pregnancies, all in patients with an LH <3 mIU/mL (P=.07). CONCLUSION(S): Low endogenous LH concentrations (<3 mIU/mL) in the late follicular phase of an IVF cycle are associated with significantly lower fertilization rates and a trend toward higher biochemical pregnancy rates. It may be of clinical benefit, when exclusively using r-hFSH in ART cycles, to add LH in the late follicular phase or to further reduce the dose of GnRH agonist.

Abortion, Spontaneous↗

Factors influencing pregnancy rates with a combined clomiphene citrate/gonadotropin protocol for non-assisted reproductive technology fertility treatment.

OBJECTIVE: To determine the effectiveness of a combined clomiphene citrate/gonadotropin protocol in a general infertility population and to evaluate factors influencing pregnancy rates obtained with this protocol. DESIGN: A retrospective chart review. SETTING; University-based infertility clinic. PATIENT(S): Two hundred forty-eight patients undergoing 658 cycles of minimal stimulation (MS) protocol from 1996-2000. INTERVENTION(S): Patients underwent treatment with clomiphene citrate and gonadotropin, often followed by intrauterine insemination. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Overall, the clinical pregnancy rate was 7.1% per cycle (n = 248 patients and 658 cycles). The age range of the patients was 24-47 years (mean +/- SD = 36.5 +/- 4.9) with 8.7% noted to have ovulatory dysfunction. Pregnancy rates varied significantly (P<.05) with patient age (9.3% in women <40 years vs. 2.4% in women > or =40), duration of infertility (9.0% in women with < or =3 years of infertility vs. 2.2% in women with >3 years of infertility) and number of follicles produced during stimulation (9.1% in women with > or =3 follicles vs. 4.6% in women with <3 follicles). CONCLUSION(S): The effectiveness of the MS protocol in a general infertility population with a predominantly ovulatory status is much less than that previously reported in a younger patient population with a significant rate of ovulatory dysfunction. This protocol does not appear to lead to pregnancy rates higher than that reported for clomiphene citrate/intrauterine insemination (IUI) cycles. The clinical pregnancy rates using a minimal stimulation protocol are particularly compromised in women over 40, those with a longer duration of infertility or those who produce few follicles during stimulation.

Adult↗

Comparison of leuprolide acetate and triptorelin in assisted reproductive technology cycles: a prospective, randomized study.

OBJECTIVE: To compare the use of two depot GnRH-a, leuprolide and triptorelin, in long-suppression GnRH-a protocols. DESIGN: Prospective, randomized study. SETTING: An IVF unit of an academic medical center.Fifty-two women who underwent controlled ovarian hyperstimulation and IVF. INTERVENTION(S): Patients were prospectively randomized to receive 3.75 mg depot formulations of either leuprolide or triptorelin on days 21-23 of the menstrual cycle. Stimulation with gonadotropins was initiated after pituitary desensitization was achieved. MAIN OUTCOME MEASURE(S): The stimulation pattern and cycle outcomes were compared between the two groups. RESULT(S): Twenty-six patients were included in each group. No significant differences were observed in the patient age, estrogen, and P levels on day of hCG administration, gonadotropin dosage, number of oocytes retrieved, fertilization rate, percentage of high-quality embryos, and number of embryos transferred. However, significantly higher clinical implantation and pregnancy rates were found in the leuprolide group compared with the triptorelin group. CONCLUSION(S): A depot preparation of leuprolide is associated with higher implantation and pregnancy rates than a depot preparation of triptorelin when it is used in the midluteal phase as part of the long-suppression GnRH-a protocol in IVF.

Adult↗

Does insurance coverage decrease the risk for multiple births associated with assisted reproductive technology?

OBJECTIVE: To determine whether insurance coverage for ART is associated with transfer of fewer embryos and decreased risk of multiple births. DESIGN: Retrospective cohort study of a population-based sample of IVF procedures performed in six U.S. states during 1998. SETTING: Three states with mandated insurance coverage (Illinois, Massachusetts, and Rhode Island) and three states without coverage (Indiana, Michigan, and New Jersey). PARTICIPANT(S): Seven thousand, five hundred sixty-one IVF transfer procedures in patients < or = 35 years of age. MAIN OUTCOME MEASURE(S): Number of embryos transferred, multiple-birth rate, triplet or higher order birth rate, and triplet or higher order gestation rate. RESULT(S): A smaller proportion of procedures included transfer of three or more embryos in Massachusetts (64%) and Rhode Island (74%) than in the noninsurance states (82%). The multiple-birth rate in Massachusetts (38%) was less than in the noninsurance states (43%). The insurance states all had protective odds ratios for triplet or higher order births, but only the odds ratio (0.2) for Massachusetts was significant. This decreased risk in Massachusetts resulted from several factors, including a smaller proportion of patients with three or more embryos transferred, lower implantation rates when three or more embryos were transferred, and greater rates of fetal loss among triplet or higher order gestations. CONCLUSION(S): Insurance appears to affect embryo transfer practices. Whether this translates into decreased multiple birth risk is less clear.

Adult↗

Assisted reproductive technology and superfetation: a case report.

This observation reports a case of human superfetation. Fertilizable oocytes and embryos were obtained after ovarian stimulation in a women already several weeks pregnant. Spontaneous monofetal pregnancy had normal development and the embryos obtained after in vitro fertilization were actually frozen.

Adult↗

Ofloxacin: the next generation of antibiotic in sperm and embryo cultures for assisted reproductive technologies.

OBJECTIVE: To analyze the effect of different concentrations of ofloxacin on sperm kinematic parameters and to determine the embryotoxicity of ofloxacin at physiologic and at 100x concentrations. DESIGN: Prospective comparative study. SETTING: Clinical and academic research environment. PATIENT(S): Pooled cryopreserved donor sperm (n = 7). INTERVENTION(S): Human sperm were processed through two-layer discontinuous Percoll gradients, and the resultant pellet was resuspended in either HEPES-buffered human tubal fluid medium containing different concentrations of ofloxacin or the control medium. After measuring the kinematic parameters, the percentages of apoptosis and viability were obtained. Next, the sperm DNA was extracted and polymerase chain reaction of beta-globin gene was performed followed by denaturing gradient gel electrophoresis. Mouse embryos recovered at the one-cell pronuclear or zygote stages were cultured in the presence or absence of ofloxacin up to the hatched blastocyst stage and differences in development were recorded. MAIN OUTCOME MEASURE(S): Sperm kinematic parameters, sperm beta-globin gene, and number of embryos reaching the hatched blastocyst stage. RESULT(S): The number of embryos exposed to control and physiologic ofloxacin concentrations showed comparable excellent growth. However, the 100x concentration significantly arrested development. Rates of sperm viability and apoptosis measured 48 hours after exposure to the above concentrations were not different from controls. No differences were noted in the sperm kinematic parameters of sperm exposed to ofloxacin concentrations (1x, 10x, and 100x) or control medium after 0, 4, and 48 hours of incubation. Denaturing gradient gel electrophoresis of beta-globin genes from DNA exposed to varying ofloxacin concentrations failed to show any point mutations. CONCLUSION(S): Ofloxacin was embryotoxic at pharmacologic concentrations (100x). At physiologic or higher concentrations, ofloxacin appears to be safe and does not affect sperm kinematic parameters when compared with controls. This may indicate that sperm motility parameters alone cannot be relied on to evaluate the effects of drugs on fertility and that in vitro embryologic studies are essential. Ofloxacin at any concentration did not alter the rates of sperm apoptosis or viability. Ofloxacin does not appear to be mutagenic as evidenced by the beta-globin gene analysis.

Analysis of Variance↗

The role of diagnostic hysteroscopy and endometrial biopsy in assisted reproductive technologies.

OBJECTIVE: To study the incidence of unsuspected endouterine abnormalities in patients for whom IVF-ET repeatedly fails. DESIGN: Prospective study. SETTING: Infertility Unit of the Department of Obstetrics and Gynecology, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. PATIENT(S): One hundred patients for whom two IVF-ET cycles failed in which > or =2 good-quality embryos were transferred. INTERVENTION(S): In-office diagnostic hysteroscopy and endometrial biopsy. MAIN OUTCOME MEASURE(S): Relation between IVF-ET failure and unsuspected endouterine abnormalities. RESULT(S): In 18 patients, hysteroscopy showed an important unsuspected endouterine abnormality. Fifteen of these patients did not become pregnant after IVF-ET, and 3 became pregnant but had a spontaneous abortion. Histologic examination of the endometrium revealed chronic endometritis in 1 patient and tuberculous endometritis in another. CONCLUSION(S): Previous studies have reported that the incidence of endouterine abnormalities is high in patients undergoing IVF-ET. Our data confirm the previous reports and lead us to conclude that diagnostic hysteroscopy should be performed on all patients before they undergo IVF-ET.

Adult↗