Brenda S. Houmard

Global Gene Expression in the Human Fetal Testis and Ovary

Abstract This study describes a temporal profile of gene expression from normal human fetal testes and ovaries. Gonads from 34 fetuses between 9 wk and 20 wk of gestation were obtained from the Department of Pathology and the Birth Defects Research Laboratory at the University of Washington. Relative transcript levels were determined using the Affymetrix Human Genome U133A Plus 2.0 arrays. Sex determination occurs in the human gonad at ∼6 wk of gestation with development of the testis driven by expression of SRY. In this study, SRY transcript was present and elevated at 9 wk of gestation in the testis but was absent in the ovary. The transcript levels of other testis-specific factors SOX9 and AMH and the steroidogenic genes CYP17A1, CYP11A1, STAR, and HSD17B3 were all significantly higher in the testis. In contrast, transcripts known to be involved in meiosis, including STRA8, SPO11, SYCP3, TEX11, TEX14, and STAG3, showed highest expression in the fetal ovary beginning at Week 12. These gene expression profiles will be a resource for understanding and defining normal gonad development and provide the opportunity to dissect abnormal development.

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.

Infertility treatment and informed consent: current practices of reproductive endocrinologists

OBJECTIVE To determine current practice patterns of obtaining informed consent for infertility treatment by reproductive endocrinologists and to assess changes in response to reports of an association between ovulation induction and ovarian cancer. METHODS Board-certified reproductive endocrinologists (n = 575) were surveyed by mail regarding how they informed patients and obtained consent for infertility treatments and how their practices had been influenced by studies suggesting a link between ovulation induction and ovarian cancer. Data were analyzed using chi2 and logistic regression analyses. RESULTS The return rate was 62.1% (357 of 575 surveys). Most respondents (92%) used discussions with physicians to inform their patients of risks and benefits of all infertility treatments. Additional means, such as audiovisual aids, were used significantly more often for assisted reproductive technologies (including intracytoplasmic sperm injection and use of donated eggs) than for less invasive therapies (31-43% versus 4-11%, P < .001). Most physicians (46-66%) used verbal consent alone for hysterosalpingogram, intrauterine insemination, and ovulation induction. Formal written consent was used significantly more often for the various assisted reproductive technologies than for hysterosalpingogram, intrauterine insemination, or ovulation induction (94-95% versus 26-44%). Although most physicians (70%) did not believe that ovulation induction increases the risk of ovarian cancer, 83% addressed this risk when obtaining consent and 47% reported changing their practices since an association was reported. Common changes included limiting length of treatment and addressing ovarian cancer risk. CONCLUSION Current practice patterns of obtaining informed consent for various infertility treatments by board-certified reproductive endocrinologists show, as expected, that informed consent is more rigorous for assisted reproductive technologies. Although most surveyed did not believe that ovulation induction increases risk of ovarian cancer, the majority of physicians addressed that risk when obtaining consent and nearly half changed their practices on the basis of a possible association.

Predicting the Onset of Menopause

The menopausal transition represents a continuum of change from regular menstrual cyclicity and fertility in the premenopausal woman to amenorrhea and loss of fecundability in the postmenopausal female. Understanding and predicting the onset of this transition has become increasingly important as the 21st century approaches. Demographic studies estimate that, in 1990, there were 467 million postmenopausal women in the world. Population projections based on these demographic studies predict that, by the year 2030, the number of postmenopausal women will increase to 1.2 billion (1). At this time, approx 47 million women will be entering menopause each year (1). Furthermore, it is estimated that women in developed countries will spend about 30 yr of their life in the postmenopausal state (2).

Hormone Replacement, Transdermal

Hormone replacement refers to the practice of supplementing in women during the menopausal years those hormones that become deficient as the ovary reaches senescence. Transdermal therapy refers to administration and absorption of these hormones via skin absorption rather than via oral administration. Hormonal supplementation may include estrogens, progestins, or testosterone derivatives.

Improved Embryo Quality and Rates of Cryopreservation With Modifications in an In Vitro Fertilization (IVF) Culture System

G1 versus HS. Materials and Methods: Oocyte cohorts from 94 retrievals were randomized to G1 or HS. Oocytes were cultured in HS from retrieval until ICSI (2–4 hrs). Following ICSI oocytes were cultured in G1 or HS until the fertilization check (16–18 hrs post-ICSI). Normally fertilized zygotes were transferred to fresh drops of the designated media and cultured until ET, the morning of day 2. Results: Study outcomes are shown below (N-retrievals; average # eggs, # inseminated (ins.) & # 2PN/retrieval; Gr 0-best to 3-poor).