Randall R. Odem

Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery

The level of tumor necrosis factor (TNF) in peritoneal fluid (PF-TNF) of 74 women undergoing laparoscopy was determined. The difference between the mean concentration of PF-TNF of women with normal pelvic anatomy and women with moderate or severe endometriosis was significant (P less than 0.01). The proportion of PF-TNF-positive women with PID and those with moderate or severe endometriosis was also significantly higher when compared to women with normal pelvic anatomy (P less than 0.05; P less than 0.02). The proportion of PF-TNF positive women among nulligravid and nulliparous women was significantly higher than that of women with two or more pregnancies (P less than 0.01) and two or more deliveries (P less than 0.005). These results indicate that the presence of PF-TNF is associated with primary infertility and endometriosis.

Mononuclear-cell immunisation in prevention of recurrent miscarriages: a randomised trial.

BACKGROUND Couples with unexplained recurrent miscarriage may have an alloimmune abnormality that prevents the mother from developing immune responses essential for the survival of the genetically foreign conceptus. Immunisation with paternal mononuclear cells is used as a treatment for such alloimmune-mediated pregnancy losses. However, the published results on this treatment are conflicting. In this study (the Recurrent Miscarriage [REMIS] Study), we investigated whether paternal mononuclear cell immunisation improves the rate of successful pregnancies. METHODS Women who had had three or more spontaneous abortions of unknown cause were enrolled in a double-blind, multicentre, randomised clinical trial. 91 were assigned immunisation with paternal mononuclear cells (treatment) and 92 immunisation with sterile saline (control). The primary outcomes were the inability to achieve pregnancy within 12 months of randomisation, or a pregnancy which terminated before 28 weeks of gestation (failure); and pregnancy of 28 or more weeks of gestation (success). Two analyses were done: one included all women (intention to treat), and the other included only those who became pregnant. FINDINGS Two women in each group received no treatment, and eight (three treatment, five control) were censored after an interim analysis. In the analysis of all randomised women who completed the trial, the success rate was 31/86 (36%) in the treatment group and 41/85 (48%) in the control group (odds ratio 0.60 [95% CI 0.33-1.12], p=0.108). In the analysis of pregnant women only, the corresponding success rates were 31/68 (46%) and 41/63 (65%; odds ratio 0.45 [0.22-0.91], p=0.026). The results were unchanged after adjustment for maternal age, number of previous miscarriages, and whether or not the couple had had a previous viable pregnancy. Similar results were obtained in a subgroup analysis of 133 couples with no previous livebirth. INTERPRETATION Immunisation with paternal mononuclear cells does not improve pregnancy outcome in women with unexplained recurrent miscarriage. This therapy should not be offered as a treatment for pregnancy loss.

Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization

OBJECTIVE To determine if follicular free fatty acid (FFA) levels are associated with cumulus oocyte complex (COC) morphology. DESIGN Prospective cohort study. SETTING University in vitro fertilization (IVF) practice. PATIENT(S) A total of 102 women undergoing IVF. INTERVENTION(S) Measurement of FFAs in serum and ovarian follicular fluid. MAIN OUTCOME MEASURE(S) Total and specific follicular and serum FFA levels, correlations between follicular and serum FFAs, and associations between follicular FFA levels and markers of oocyte quality, including COC morphology. RESULT(S) Predominant follicular fluid and serum FFAs were oleic, palmitic, linoleic, and stearic acids. Correlations between follicular and serum FFA concentrations were weak (r=0.252, 0.288, 0.236, 0.309, respectively for specific FFAs; r=0.212 for total FFAs). A receiver operating characteristic curve determined total follicular FFAs≥0.232 μmol/mL distinguished women with a lower versus higher percentage of COCs with favorable morphology. Women with elevated follicular FFAs (n=31) were more likely to have COCs with poor morphology than others (n=71; OR 3.3, 95% CI1.2-9.2). This relationship held after adjusting for potential confounders, including age, body mass index, endometriosis, and amount of gonadotropin administered (β=1.2; OR 3.4, 95% CI 1.1-10.4). CONCLUSION(S) Elevated follicular FFA levels are associated with poor COC morphology. Further work is needed to determine what factors influence follicular FFA levels and if these factors impact fertility.

Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome

OBJECTIVE To determine whether morbid obesity is associated with decreased pregnancy and live birth rates after IVF in women with polycystic ovary syndrome (PCOS). DESIGN Retrospective cohort study. SETTING University-based fertility center. PATIENT(S) Seventy-two women with PCOS who completed their first IVF cycle between 2001 and 2006. INTERVENTION(S) Outcomes of IVF were compared between women with a body mass index (BMI) of <40 kg/m(2) vs. those with a BMI of > or =40 kg/m(2). MAIN OUTCOME MEASURE(S) Clinical pregnancy rate, live birth rate. RESULT(S) Morbidly obese women with PCOS (n = 19) had significantly lower clinical pregnancy rates after IVF than patients with PCOS who were not morbidly obese (n = 53) (32% vs. 72%, relative risk 0.44, 95% confidence interval 0.22-0.87). Their live birth rates were lower too, although this difference was not statistically significant (32% vs. 60%, relative risk 0.52, 95% confidence interval 0.26-1.05). CONCLUSION(S) Morbid obesity is associated with lower pregnancy rates in women with PCOS after IVF, raising the question of whether weight loss may improve IVF success rates for morbidly obese PCOS patients.

Endometrial thickness is a valid monitoring parameter in cycles of ovulation induction with menotropins alone

OBJECTIVE To evaluate the ability of an ultrasound (US)-measured periovulatory endometrial thickness to predict conception in hMG-stimulated cycles. DESIGN Retrospective. SETTING A university-based tertiary practice. PATIENTS One hundred twelve patients undergoing 292 cycles of ovulation induction with hMG alone. MAIN OUTCOME MEASURES A periovulatory transvaginal US measurement of endometrial thickness was obtained during cycles of ovulation induction with hMG alone. Clinical pregnancy was defined by fetal cardiac activity. Sensitivity and false-positive rates for multiple discriminatory values of endometrial thickness were calculated and a relative operating characteristic (ROC) curve was constructed to evaluate the performance of this test as a predictor of pregnancy. RESULTS Thirty-eight of 292 cycles resulted in pregnancy. Conception and nonconception cycles showed similar demographics, diagnoses, peak E2, maximum number of follicles, midluteal P, and mean endometrial thickness. Ovulatory dysfunction was a more frequent diagnosis in the conception group. Relative operating characteristic analysis for endometrial thickness as a predictor of pregnancy yielded an area under the curve of 0.623 +/- 0.049 (mean +/- SD). CONCLUSION Endometrial thickness is a valid screening test for conception outcome in cycles stimulated with hMG. A periovulatory endometrial thickness > or = 10 mm defined 91% of conception cycles. No pregnancy occurred when the endometrium measured < 7 mm.

Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro fertilization/intracytoplasmic sperm injection cycles

To determine the impact of maternal metabolic state on oocyte development in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), we retrospectively analyzed a cohort of women with PCOS undergoing IVF/ICSI from 2008-2009 in a university-based fertility center. We determined that women with PCOS and obesity have smaller oocytes than control subjects, and that when further subdivided by body mass index, both PCOS and obesity independently influence oocyte size.

Qualitative point-of-care and over-the-counter urine hCG devices differentially detect the hCG variants of early pregnancy

BACKGROUND Qualitative point-of-care (POC) tests for human chorionic gonadotropin (hCG) vary in their ability to detect purified hCG variants and there is data to suggest that over-the-counter (OTC) devices might also display similar variability. This could potentially influence the detection of urine hCG in early pregnancy. METHODS Six OTC devices were tested for their ability to detect 5 hCG variants. Ten early pregnancy urine specimens were selected for their diverse expression of hCG variants. The samples were tested with 6 brands of POC and 6 OTC devices. RESULTS OTC devices consistently recognized intact hCG, hCGn, and hCGbeta. hCGbetan was consistently recognized by 4 out of 6 brands. One brand inconsistently recognized hCGbetacf. OTC and POC devices varied greatly in their ability to detect hCG in early pregnancy urine, despite the fact that urine samples were adjusted to the same intact hCG concentration. Interestingly, we found that the OTC devices had better analytical sensitivity than the POC devices. Clinitest and First Response demonstrated the lowest hCG detection limits for POC and OTC devices, respectively. CONCLUSIONS Both OTC and POC devices are capable of detecting hCG concentrations in early pregnancy urine, and OTC devices demonstrated better analytical sensitivity relative to POC devices.

A prospective, randomized, double-blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization

OBJECTIVE To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida (ZP). DESIGN Prospective, randomized, double-blinded, crossover study. SETTING University-based infertility center. PATIENT(S) One hundred twenty-one women less than 38 years of age, undergoing IVF at Washington University between April 2004 and February 2007, with ZP thickness > or =13 microm for any embryos. INTERVENTION(S) Measurement of ZP thickness in embryos undergoing IVF; randomization of women with embryos with ZP thickness > or =13 microm to no procedure or assisted hatching performed by acidic Tyrodes solution. MAIN OUTCOME MEASURE(S) Clinical intrauterine pregnancy rate, implantation rate, spontaneous pregnancy loss, and live birth rate. RESULT(S) Baseline characteristics and ZP thickness were not significantly different between the two study arms (hatched and unhatched). No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy (47% vs. 50% respectively) or live birth (46% vs. 45% respectively). Further, no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions, monozygotic twinning, dizygotic twinning, chromosomal abnormalities, or ectopic gestations. In addition, mean ZP thickness did not have a significant effect on pregnancy. CONCLUSION(S) In patients younger than 38 years with embryos with ZP thickness of > or =13 microm, assisted hatching does not improve the rates of implantation, clinical pregnancy, or live birth, and thus does not appear to offer any benefit to patients in this age group undergoing IVF.

Elevated serum alpha-linolenic acid levels are associated with decreased chance of pregnancy after in vitro fertilization

OBJECTIVE To analyze relationships between serum free fatty acid (FFA) concentrations and pregnancy. DESIGN Prospective cohort. SETTING University hospital. PATIENT(S) Ninety-one women undergoing IVF. INTERVENTION(S) Serum was analyzed for total and specific serum FFAs, including myristic, palmitic, stearic, oleic, linoleic, and α-linolenic acids. MAIN OUTCOME MEASURE(S) Univariate analyses were used to identify specific FFAs and other factors associated with pregnancy after IVF. Logistic regression was performed modeling relationships between identified factors and chance of pregnancy. RESULT(S) In unadjusted analyses, women with elevated serum α-linolenic acid (ALA) levels (highest quartile) demonstrated a decreased chance of pregnancy compared with women with the lowest levels (odds ratio 0.24, 95% confidence interval 0.052-0.792). No associations between other FFAs and pregnancy were identified. In a multivariable regression model, associations between elevated serum ALA levels and decreased chance of pregnancy remained after adjusting for patient age, body mass index, and history of endometriosis or previous live birth (adjusted odds ratio 0.139, 95% confidence interval 0.028-0.686). CONCLUSION(S) Elevated serum ALA levels are associated with decreased chance of pregnancy in women undergoing IVF. Further work is needed to determine whether ALA is involved in early reproductive processes and whether the relationship between ALA and pregnancy is associated with excess ALA intake, impaired ALA metabolism, or both.

In vitro fertilization after bariatric surgery

Few data exist regarding IVF in women who have undergone bariatric surgery. Our experience with five patients suggests that IVF is a safe and effective fertility treatment for these women, although special considerations should be made when treating patients who have undergone bariatric surgery. Considering the type of bypass procedure the patient underwent is particularly important should a patient develop concerning symptoms during her IVF cycle.