Alice Rhoton-Vlasak

Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding

OBJECTIVE To determine the expression of matrix metalloproteinase (MMP-26) and tissue inhibitor of MMP (TIMP) in the endometrium of women with normal menstrual cycles compared with users of levonorgestrel implants. DESIGN Prospective observational study. SETTING Academic research center. PATIENT(S) Fifty patients with normal menstrual cycles who requested permanent surgical sterilization (tubal ligation) and 35 users of levonorgestrel implants. INTERVENTION(S) Endometrial biopsy. MAIN OUTCOME MEASURE(S) Expression of MMP-26, TIMP-3, and TIMP-4 by immunohistochemistry and semiquantitative analysis of staining intensity by using the H score. RESULT(S) Endometrium from women with a normal menstrual cycle and users of levonorgestrel implants expresses MMP-26, TIMP-3, and TIMP-4. These substances are present in various types of endometrial cells; expression is strongest in surface and glandular epithelial cells, followed by vascular endothelial and endometrial stromal cells. Inflammatory and immune-related cells also stained strongly for MMP-26 and TIMPs. Semiquantitative analysis of the staining intensity of endometrial epithelial and stromal cells indicated that expression of MMP-26, TIMP-3, and TIMP-4 peaks during the early to mid-luteal phase. Expression of MMP-26 is elevated in users of levonorgestrel implants who experienced irregular uterine bleeding. CONCLUSION(S) Endometrial expression of MMP-26 and TIMP-4 is present throughout the menstrual cycle and is elevated during the early to mid-luteal phase in normally cycling women. Further elevations in MMP-26 are seen in users of levonorgestrel implants who experience irregular uterine bleeding. These substances thus seem to play a role in hormonal regulation and endometrial tissue remodeling.

Placental site trophoblastic tumor: Human placental lactogen and pregnancy-associated major basic protein as immunohistologic markers

Placental site trophoblastic tumor (PSTT) consists of a neoplastic proliferation of intermediate or extravillous trophoblast (also known as X cells). Pregnancy-associated major basic protein (pMBP) is a marker for placental intermediate trophoblast. We compared the distribution of pMBP and human placental lactogen (hPL) in 24 PSTT and 3 exaggerated placental site (EPS) specimens using two distinct immunohistologic methods. Statistical analyses were used to compare staining intensities in metastatic and nonmetastatic lesions. By immunofluorescence, 77% of the PSTT specimens and 100% of the EPS specimens stained with antibodies to pMBP, and the pMBP was localized in intermediate trophoblast and surrounding extracellular areas. By immunohistochemistry, 78% of the PSTT specimens and 100% of the EPS specimens stained for pMBP with a pattern comparable with that of immunofluorescence. Likewise, by immunohistochemistry, hPL stained 96% of the PSTT specimens and 100% of the EPS specimens. Immunohistochemical staining intensities for pMBP and hPL correlated (r2 = +.24; P = .013), but hPL staining was mainly confined to intermediate trophoblast and was more intense. Anti-pMBP tended to stain metastatic PSTT weakly. Thus, pMBP is a useful marker for intermediate trophoblast tumors and could help distinguish these from other forms of trophoblastic disease.

Infections and infertility

Infertility affects 10-15% of all couples. Pelvic infections are an important cause of infertility, primarily as a result of tubal damage. Damage to the fallopian tubes from infections may be due to adhesions, tubal mucosal damage, or tubal occlusion that interferes with normal ovum transport. The infections most commonly related to infertility include gonorrhea, chlamydia, and pelvic inflammatory disease. Tuberculosis also is a common cause of infertility in Third World nations. Sequelae resulting from these infections include ectopic pregnancy, infertility, chronic pelvic pain, hydrosalpinx, and tuboovarian abscess. Neisseria gonorrhoeae and Chlamydia trachomatis are the primary causes of pelvic inflammatory disease. Chlamydial infections may be asymptomatic, and the resulting salpingitis is often referred to as silent pelvic inflammatory disease. Polymicrobial infection with other organisms such as anaerobes or facultative aerobes may be initiated by gonorrhea, chlamydia, or both. Early recognition of infection, prompt institution of appropriate antibiotic therapy, and proper follow-up are important to prevent the sequelae of pelvic inflammatory disease. Surgical intervention may be needed to treat immediate or long-term sequelae of infection. Prevention of pelvic infections should be a high priority. Fortunately, treatment options such as tubal microsurgery and assisted reproductive technologies offer couples reproductive options even when infertility occurs as the result of a previous pelvic infection.

Laparoscopic Ovarian Transposition Before Pelvic Cancer Treatment: Ovarian Function and Fertility Preservation

Survivors of pelvic cancer treatment live with the ramifications of pelvic radiation for many years after their cure. Several options are available to preserve ovarian function and fertility in reproductive age women undergoing pelvic radiation. Laparoscopic ovarian transposition is an under-utilized, yet fairly simple surgical procedure to relocate the ovaries away from the radiation field. Although randomized-controlled trials on the outcomes of ovarian transposition are scarce, there is a growing body of evidence on the risks and benefits of this procedure, in terms of prevention of premature ovarian failure, and potentially preserving fertility. In this review, we summarize the available data on the indications, patient selection and outcomes of ovarian transposition, as well as illustrate the technique of the procedure.

An assessment of current clinical attitudes toward letrozole use in reproductive endocrinology practices

OBJECTIVE To assess the clinical use and practice attitudes among Society for Assisted Reproductive Technology (SART) members regarding the use of letrozole for ovulation induction and infertility treatment. DESIGN The SART clinic physicians were mailed a cover letter and consent form, a two-page survey, and return envelope. The surveys were returned and analyzed using descriptive statistics. SETTING Not applicable. PATIENT(S) None. INTERVENTION(S) A 13-question survey. MAIN OUTCOME MEASURE(S) Reproductive endocrinology and infertility physicians use patterns and attitudes regarding letrozole. RESULT(S) A total of 77.9% of physician prescribe letrozole. Of those who do not, 32.4% cited concern about the US Food and Drug Administration warning, 35.1% cited satisfaction with current medications, 25.7% cited both reasons, and 6.8% cited no experience with letrozole. Physicians (11.5%) were unaware of the US Food and Drug Administration warning. Physicians (99.7%) were aware that ovulation induction is an off-label use of letrozole. The most common use was for ovulation induction in patients with polycystic ovary syndrome (PCOS). Physicians (14.9%) prescribe letrozole as first-line ovulation therapy prior to clomid, 47.9% use for clomid failures, and 25.7% reported use in both situations. CONCLUSION(S) Most physicians surveyed use letrozole for ovulation induction despite the current US Food and Drug Administration warning. Even when accounting for nonrespondents, more than 25% of physicians indicated success with letrozole use. Questions regarding doses and clinical concerns about letrozole revealed no standardized manner of letrozole administration despite wide interest, therefore additional research is warranted.

Localization and cellular distribution of pregnancy-associated plasma protein-A and major basic protein in human ovary and corpora lutea throughout the menstrual cycle

OBJECTIVE To assess the expression and cellular distribution of pregnancy-associated plasma protein-A (PAPP-A) and major basic protein (MBP) in human ovarian tissue during the menstrual cycle. DESIGN Ovarian tissues (n = 50) and corpora lutea (n = 18) were obtained from patients undergoing hysterectomy/oophorectomy for benign conditions and tissue sections were immunostained for MBP and PAPP-A. SETTING University medical center. INTERVENTION(S) Immunostaining of tissue sections using antibodies to PAPP-A and MBP. MAIN OUTCOME MEASURE(S) Microscopic evaluation to assess the presence, distribution, and cellular co-localization of MBP and PAPP-A and to describe any variations in their expression during the menstrual cycle. RESULT(S) Major basic protein (MBP) is found in several ovarian cell types throughout the menstrual cycle. The MBP immunostaining of ovarian follicles varied depending on the size, with primordial follicles staining in the ooplasm with a lack of staining in the granulosa and theca cells. In the intermediate/mature follicles, MBP was immunolocalized in theca, but not in granulosa cells except in the mature follicles. Pregnancy-associated plasma protein-A (PAPP-A) was immunolocalized in primordial follicle ooplasm, theca externa of intermediate/mature follicles, and in granulosa cells with increased intensity as luteinization progressed. The luteal tissue is the major site of MBP and PAPP-A with highest intensity found during the midluteal phase associated with both small and large luteal cells. CONCLUSION(S) The expression and distinct pattern of MBP and PAPP-A cellular localization in human ovarian tissue during folliculogenesis and in luteal tissue suggest that their individual and combined actions in a cell specific fashion may play a role in growth and differentiation of theca, granulosa, and luteal cells.

Validity of a rapid assay for antisperm antibodies in semen

OBJECTIVE To determine the validity of a rapid assay for antisperm antibodies in semen. DESIGN Prospective comparison of the results of standard and rapid antisperm antibody assays performed simultaneously. SETTING Tertiary care infertility center. PATIENT(S) Couples who presented for infertility evaluation. INTERVENTION(S) Semen analysis and measurement of antisperm antibodies in semen using a standard and a rapid immunobead binding test (IBT). MAIN OUTCOME MEASURE(S) [1] Comparison of sperm parameters between semen-containing antisperm antibodies and semen free of antisperm antibodies. [2] Validation of the rapid test by calculation of sensitivity, specificity, positive and negative predictive values of the rapid assay using the standard assay as a gold standard. [3] Cost comparison of the standard and rapid test. RESULT(S) [1] Nine semen specimens with antisperm antibodies had a significantly lower sperm concentration, motility, and total motile fraction compared to 44 specimens without antisperm antibodies. Also, specimens with antisperm antibodies had a significantly higher percentage of vibratory sperm and percent of bound antisperm antibodies. The strict morphology, liquefaction time, semen volume, and white blood cell concentration were no different between the two groups. [2] Using a threshold of > or =12% of bound antisperm antibodies in the rapid assay, the sensitivity, specificity, positive and negative predictive values of the test are 100% when correlated with a threshold of > or =20% in the standard assay. Increasing the threshold in the standard assay decreases the specificity and positive predictive value of the rapid assay but not the sensitivity and the negative predictive value. [3] The cost of the rapid assay was 16% that of the standard test and its performance took 20% of the time it took to set and perform the standard test. CONCLUSION(S) A rapid test for antisperm antibodies is valid, reliable, and more cost and labor effective than a standard IBT.

Pregnancy rates in varying age groups after in vitro fertilization: a comparison of follitropin alfa (Gonal F) and follitropin beta (Follistim).

OBJECTIVE Our purpose was to assess the efficacy of two recombinant follicle-stimulating hormones, follitropin beta (Follistim, Organon, West Orange, NJ) and follitropin alfa (Gonal F, Serono, Norwell, Mass) on pregnancy rates in varying age groups of women undergoing in vitro fertilization (IVF). STUDY DESIGN Three hundred sixty-five IVF cycles were retrospectively compared, 233 by use of follitropin beta and 132 by use of follitropin alfa, both after gonadotropin-releasing hormone agonist down-regulation. Assignment to each medication was indiscriminate. The primary outcome measured was pregnancy evidenced by fetal heartbeat on ultrasonography. Secondary outcomes included days of stimulation, ampules per patient cycle, estradiol level on the day of human chorionic gonadotropin administration, total follicles present on the day of human chorionic gonadotropin administration, follicles greater than 14 mm, oocytes retrieved, mature eggs, fertilization rate, and embryos transferred. Outcomes were stratified by age, including women less than 36 years old, 36 to 39 years old, and more than 39 years old. RESULTS There was no significant difference between follitropin beta and follitropin alfa in either the primary or secondary outcomes, although the pregnancy rate was significantly decreased with advancing age. CONCLUSION Success rates are similar, when stratified by age, in women undergoing IVF with either follitropin beta or follitropin alfa.

Comparison of multiple non‐invasive methods of measuring cardiac output during pregnancy reveals marked heterogeneity in the magnitude of cardiac output change between women

Various non‐invasive methods are available to measure cardiac output (CO) during pregnancy. We compared serial measures of CO using various methods to determine which provided the least variability. Ten patients with spontaneous pregnancy had estimation of CO at baseline prior to becoming pregnant and at the end of the first and third trimesters. Echocardiographic data were used to estimate CO using the Teichholz method, Simpsons biplane method, and the Doppler determined velocity time integral (VTI) method. In addition, a Bioz Dx device was used to estimate CO by impedance cardiography. CO estimated with the VTI method had the lowest beat‐to‐beat variability. CO estimated with the VTI method was higher than CO estimated with the 2D‐Teichholz method and Simpsons method. The percent change in CO during pregnancy was similar for all echo methods (VTI, Teichholz, and Simpsons biplane). Baseline CO determined with impedance cardiography was higher than CO determined with the VTI method. However, change in CO during pregnancy was significantly lower when measured with impedance cardiography. There was marked heterogeneity in the degree of rise in CO during the first trimester (−3 to 55%). The wide variation in the gestational rise in CO was unexpected, and at least in part secondary to variable increase in heart rate. We recommend the use of the Doppler determined VTI method for the estimation of CO in pregnancy.

Viral influenza in women

Abstract Viral influenza is an acute respiratory infection caused by strains of the orthomyxovirus. The influenza viruses are negative-stranded RNA viruses of three major antigenic types—A, B, and C. Influenza A and B viruses are most important in human disease and have been studied far more extensively than influenza C viruses. Influenza A and B viruses are characterized based on their hemagglutinin and neuraminidase antigens. Immunity to these antigens, especially to the hemagglutinin, reduces the likelihood of infection and lessens the severity of disease if infection occurs. Because of this antigenic variation, major epidemics of respiratory disease caused by new variants of influenza continue to occur. The antigenic characteristics of circulating strains provide the basis for selecting the virus strains included in each year’s vaccine. Viral influenza may cause serious morbidity, especially in adults, and result in prolonged absences from work. Mortality may occur as a result of secondary infection with bacterial pneumonia or other complications, such as myocarditis, pericarditis, aseptic meningitis, and postinfection neuritis. Two measures available that can reduce the impact of influenza are immunoprophylaxis with inactivated vaccine and chemoprophylaxis or therapy with an antiviral drug such as amantadine or rimantadine. Intensive supportive therapy with antipyretics, analgesics, and fluid repletion also is important. Nonpregnant patients may be treated with amantadine to reduce the severity of symptoms. Amantadine or rimantadine are relatively contraindicated in pregnancy. The best method of prevention in pregnant women is the influenza vaccine.