Barry R. Witt

Abnormal sperm morphology is highly predictive of pregnancy outcome during controlled ovarian hyperstimulation and intrauterine insemination

AbstractPurpose: The purpose of this study was to assess the predictive value of a modified form of Krugers strict criteria for sperm morphology for pregnancy outcomes after intrauterine insemination (IUI) and controlled ovarian hyperstimulation (COH) in the presence of normal sperm concentration and motility. Materials and Methods: A retrospective review of 42 couples undergoing COH/IUI was stratified by favorable or unfavorable sperm morphology. End points were pregnancy or failure of treatment as defined by four or more cycles of COH/IUI without pregnancy. Results: An unfavorable morphology (<4%) was highly predictive of failure during COH-IUI (94.45%; 17/18). A normal PIF was a sensitive indicator of those patients who became pregnant (93.8%; 15/16) and had a fair specificity for failure to achieve pregnancy after four cycles of treatment (65.4%; 17/26). Couples with a favorable sperm morphology were 28.3 times as likely to achieve a pregnancy within four cycles of treatment as those with unfavorable sperm morphology [95% confidence limits, 3.2 to 250.5; P<0.001]. Conclusions: Abnormal strict morphologic assessment is both sensitive and specific for pregnancy outcomes in couples undergoing COH/IUI. Couples with persistently unfavorable sperm morphology should be counseled appropriately and would be better served by more aggressive treatment with in vitro fertilization and embryo transfer.

Levels of interferon-Γ and tumor necrosis factor-α in sera and cervical mucus of fertile and infertile women: implication in infertility

Concentrations of two immune cytokines, namely interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha), were determined in the sera and cervical mucus samples of fertile (n = 16), idiopathic infertile (n = 44), and immunoinfertile women (n = 45) to investigate their role, if any, in female infertility. Sera of idiopathic infertile women demonstrated significantly (P 0.05) correlate (r = 0.12-0.43) with the concentrations in cervical mucus, when all the three groups were compared together. However, when the serum levels were compared with the cervical mucus concentrations by condition, only the idiopathic infertile group showed a significant (P = 0.005) correlation (r = 0.70). Serum levels of TNF-alpha did not differ significantly (P > 0.05) among three groups of women. Cervical mucus concentrations of TNF-alpha, however, varied among groups with levels being significantly (P = 0.04) higher-in idiopathic infertile women compared with fertile controls and in immunoinfertile women significantly (P = 0.0007) higher than in fertile controls as well as idiopathic infertile women. TNF-alpha levels in serum correlated (r = 0.65) significantly (P < 0.001) with the concentrations in cervical mucus when all the three groups were compared together or individually by infertility condition. These findings suggest the involvement of cytokines in infertility, and thus may have potential applications in diagnosis and treatment of female infertility.

Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation.

A comparative study of four treatment regimens for women with a history of poor response to controlled ovarian hyperstimulation (COH) during attempts at in vitro fertilization (IVF) and embryo transfer suggested the feasibility of pretreatment with oral contraceptives (OCs). The 60 women enrolled in the study exhibited one or more of the following in an initial stimulated IVF cycle: three or fewer dominant follicles recruited, serum estradiol levels of 300 pg/ml or below, and/or a spontaneous luteinizing hormone (LH) surge prior to oocyte retrieval. Study subjects were assigned to one of four protocols: Group I--OCs for 3 weeks followed by COH; Group II--luteal phase leuprolide acetate with subsequent COH; Group III--short-flare Lupron with subsequent COH; and Group IV--COH alone. COH consisted of 150 IU/day of pure follicle-stimulating hormone (pFSH) and 150 IU/day of human menopausal gonadotropin (hMG). The mean age of women in each group ranged from 36.0 to 38.8 years. There were no significant differences among groups in terms of number of days of stimulation, total ampoules of hMG and pFSH required, peak serum estradiol and progesterone, number of oocytes retrieved and fertilized, and embryos transferred. However, the pregnancy rate was significantly higher (p 0.05) in Group I (9/30, 30%) than in Group II (2/32, 6%), Group III (0/11, 0%), and Group IV (0/10, 0%). The good outcome associated with OC pretreatment may reflect production or alterations of local ovarian growth factors and/or changes in endometrial expression. Administration of exogenous estrogen may be particularly beneficial for perimenopausal women in their forties with ovarian follicular depletion.

Colony stimulating factor-1 in human follicular fluid

OBJECTIVE To evaluate colony stimulating factor-1 (CSF-1) concentrations in serum and follicular fluid (FF) at the time of oocyte retrieval and to test for presence of messenger RNA (mRNA) for CSF-1 and its receptor, c-fms, in FF cells. DESIGN Collection of serum and FF at the time of oocyte retrieval. SETTING A university IVF program. PATIENT(S) Forty-five women undergoing oocyte retrieval for IVF. INTERVENTION(S) Serum and FF were obtained from 24 women, and FF only was obtained from 21 women. MAIN OUTCOME MEASURE(S) Colony-stimulating factor-1 concentrations were determined by RIA, and the presence of mRNA for CSF-1 and c-fms was determined by reverse transcriptase-polymerase chain reaction. RESULT(S) Mean FF concentrations of CSF-1 were significantly higher than mean serum levels (10.0 +/- 1.3 and 3.6 +/- 0.3 (+/-SE) ng/mL, respectively). Colony-stimulating factor-1 and c-fms message were detected in FF cells, and alternatively spliced forms of CSF-1 message were present. CONCLUSION(S) The presence of CSF-1, a primary regulator of tissue macrophages, in FF, and the presence of mRNA for CSF-1 and its receptor c-fms in FF-derived cells, suggest a role for this growth factor in ovarian function.

Clinical Assisted Reproduction: Hypothalamic-Pituitary Suppression with Oral Contraceptive Pills Does Not Improve Outcome in Poor Responder Patients Undergoing In Vitro Fertilization-Embryo Transfer Cycles

AbstractPurpose: To evaluate and compare the use of OCP with GnRHa for hypothalamic-pituitary suppression in poor responder IVF patients. Methods: Retrospective analysis of IVF-ET cycles of poor responders. Hypothalamic-pituitary suppression with OCP (Group I, n = 29) or GnRHa (Group II, n = 52), followed by stimulation with gonadotropin, oocyte retrieval, and embryo transfer. Baseline characteristics and cycle outcomes were compared. Results: 73 women underwent 81 cycles from 1/1/1999 to 1/1/2000. Baseline characteristics were similar. 31/81 (38%) cycles were cancelled (Group I, 14/29 (48%) vs. Group II, 17/52 (33%), NS). Cycle outcomes including amount of gonadotropin, number of eggs retrieved, number of embryos transferred, and embryo quality were similar. Patients in Group I required fewer days of stimulation to reach oocyte retrieval. Pregnancy outcomes were similar in the two groups. Conclusion: Our retrospective analysis revealed no improvement in IVF cycle outcomes in poor responders who received OCPs to achieve hypothalamic-pituitary suppression instead of GnRHa.

Is affect associated with infertility treatment outcome

Infertility is a unique diagnosis consisting of a functional medical aspect and a psychologic recognition on the part of the patient that not being able to have a child is a life goal problem. In previous unpublished research performed by the authors, it was noted that approximately one third of patients who were initially identified as part of a research study had left treatment before the study was completed. Similar statistics were previously noted by Strauss et al. (1) and Camilleri (2). The aim of this study was to observe the correlation between psychologic effect and patient treatment status over time, and to determine why so many patients failed to follow through with treatment recommendations.

Basal serum follicle stimulating hormone (FSH) and estradiol levels as predictors of pregnancy in unstimulated donor insemination cycles

PurposeThe purpose of this study was to evaluate the utility of basal serum follicle stimulating hormone and estradiol levels in predicting pregnancy in women undergoing artificial insemination with donor sperm for severe male factor infertility.MethodA retrospective chart review of 48 women who had at least 2 cycles of artificial insemination with donor sperm and who had undergone testing for basal serum follicle stimulating hormone and estradiol levels prior to or during therapy.ResultsThere was no difference in age or mean basal serum follicle stimulating hormone between women who conceived (clinical pregnancy) and those who did not. Women who conceived had significantly lower mean serum basal estradiol levels (P = 0.02) and significantly fewer numbers of treatment cycles (P = 0.041). The highest pregnancy rate was among those women with normal basal serum follicle stimulating hormone and estradiol levels. Receiver operating characteristic curve analysis revealed basal serum estradiol to be a more reliable predictor of pregnancy than follicle stimulating hormone.ConclusionsBasal serum follicle stimulating hormone and estradiol levels may be useful in predicting success with artificial insemination with donor sperm. It may be useful to obtain basal serum follicle stimulating hormone and estradiol prior to initiating artificial insemination with donor sperm.

Day 6 Estradiol Level Predicts Cycle Cancellation Among Poor Responder Patients Undergoing In Vitro Fertilization—Embryo Transfer Cycles Using a Gonadotropin-Releasing Hormone Agonist Flare Regimen

AbstractPurpose: To compare two GnRHa flare protocols among poor responders undergoing IVF-ET and to evaluate if a Day 6 estradiol level can predict outcome. Methods: Retrospective analyses of GnRHa flare IVF cycles among poor responders. Group A (“miniflare,” N = 36) 40 μg GnRHa s.c. b.i.d. from Day 3; Group B (“standard flare,” N = 24) 1 mg GnRHa on Days 2–3; 0.5 mg GnRHa from Day 4. ROC analysis was performed to find a Day 6 estradiol value that is predictive of cycle outcome. Results: With the standard flare, patients required less gonadotropins and tended to have fewer cancellations and higher pregnancy rates. A Day 6 estradiol level ≤75 pg/mL was predictive of cycle cancellation, but not of pregnancy outcome. Conclusions: Standard GnRHa flare offers some advantages over the miniflare. Day 6 estradiol ≤75 pg/mL is predictive of cycle cancellation. When the estradiol level is low on Day 6 (no flare), early cancellation should be considered.

Choices: Biomedical Ethics and Women's Health: Multiple Pregnancies and Assisted Reproductive Technologies

We are in the midst of an historically unprecedented increase in the incidence of multiple pregnancy. Throughout the 20th century, infant mortality has declined more than 90%, to 7.2/1000 live births. However, in the latter part of the 20th century, the decline in neonatal mortality is more attributable to improved rates of survival of low birth weight infants than to the reduction in incidence of low birth weight. Low birth weight is associated with longterm effects, such as neurological disorders, learning disabilities, and delayed development. Multiple births are 8 times more likely to be low birth weight than are singleton births. Half of all twins and 90% of all triplets and higher multiple births are low birth weight. Two possible sources of the observed increase in multiple births are increasing use of ovulation induction and increasing use of assisted reproductive technology (ART) procedures to treat infertility. In 1990, the Centers for Disease Control and Prevention (CDC) estimated that liveborn...

Potential limiting factors in resident training for laparoscopic management of ectopic pregnancies

STUDY OBJECTIVE To evaluate resident exposure and training in operative laparoscopic management of ectopic pregnancy (EP). DESIGN A review and comparison of the profile and management of consecutive series of patients with EP in two different clinical settings. SETTING A university-affiliated obstetrics and gynecology residency program caring for indigent women, and a private, office-based infertility practice. PATIENTS Fifty-three consecutive patients with EP treated surgically in an infertility practice (group 1) were compared with 68 such women managed in a residency program (group 2). RESULTS Evaluation at the time of hospital admission confirmed significantly lower systolic and diastolic blood pressures (mean +/- SD 106.2 +/- 12.2 mm Hg vs 114.8 +/- 9.1 and 61.1 +/- 14.4 mm Hg vs 71.7 +/- 11.8 mm Hg, p <0.05) and hemoglobin (10.9 +/- 2.7 g/dl vs 12.2 +/- 2.2 g/dl, p <0.05), and higher pulse rates (96.1 +/- 12.1 bpm vs 84.0 +/- 7.7 bpm, p <0.01) for groups 2 and 1, respectively. The mean gestational age at diagnosis was greater in group 2 (52.1 +/- 14.8 days) than in group 1 (46.7 +/- 11.1 days, p <0.05). That the overall clinical picture in group 2 was more serious was confirmed by a larger mean gestational mass (4.4 +/- 3.1 cm vs 2.8 +/- 2.6 cm, p <0.01), more frequent rupture (69% vs 21%, p <0.01), and a larger hemoperitoneum (547 +/- 488 ml vs 215 +/- 202 ml, p <0. 05). Similarly, 49% of group 2 patients required postoperative or intraoperative blood transfusion, compared with 13% of group 1 (p <0. 01). Forty-four of 53 women in group 1 were managed laparoscopically (83%), whereas only 16 (24%) in group 2 were so treated (p <0.05). CONCLUSION Patients in group 2 were more hemodynamically compromised, had more advanced gestations, and had more ruptured EPs, leading to decreased opportunities for laparoscopic management. Active resident participation in operative management of nonindigent women with EP may be necessary to ensure appropriate training.