Early predictive biomarkers for postpartum depression point to a role for estrogen receptor signaling.

BACKGROUND: Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort. METHOD: We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R. RESULTS: We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD. CONCLUSIONS: These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.

Evaluation of the prognosis of in vitro fertilization pregnancies with initially low serum human chorionic gonadotropin levels.

OBJECTIVE: The objective of this study was to investigate the prognostic significance of initially low serum early human chorionic gonadotropin levels in in vitro fertilization pregnancies that progress to an intrauterine gestational sac. STUDY DESIGN: This retrospective cohort study compared 65 in vitro fertilization pregnancies with an initial human chorionic gonadotropin value at 4 weeks of < or =20 mIU/mL with 130 pregnancies with human chorionic gonadotropin values >20 mIU/mL. All pregnancies had a singleton intrauterine sac at 6 weeks' gestational age. Spontaneous abortion rates and pregnancy complications were compared. RESULTS: Women with a low initial serum human chorionic gonadotropin level showed a statistically significant increase in first-trimester pregnancy loss (36.5% vs 9.2%; odds ratio, 5.7; 95%; confidence interval, 2.6, 12.4; P <.0001). Once pregnancies progressed to 13 weeks, there were no significant differences. CONCLUSIONS: In vitro fertilization pregnancies with a low initial human chorionic gonadotropin value, despite progressing to a gestational sac, are at an increased risk of spontaneous abortion.

Folic acid. Preconception knowledge and use by infertile women.

OBJECTIVE: To assess knowledge of preconception folic acid intake (PFAI) and its use by infertile women and to compare it to results from a national survey of reproductive-age women. STUDY DESIGN: New patients presenting to a reproductive medicine practice were surveyed regarding their knowledge and use of PFAI. Results were compared to those of a national survey of reproductive age women. RESULTS: Eighty-six women were surveyed. Infertile women were more aware of the benefits of PFAI than the control population (65% vs. 13%) and used it more frequently (52% vs. 29%). Although infertile women knowledgeable about PFAI were more likely to take folic acid (chi 2 = 24.90, P < .001), 30% of women who were aware of the benefits of PFAI did not take it. CONCLUSION: Preconception folic acid knowledge and use were higher among infertility patients presenting to a reproductive medicine practice than in the general population. Nonetheless, in this highly motivated population, only half were taking folic acid, and knowledge alone did not ensure usage. To effectively decrease the incidence of neural tube defects, food fortification may be more effective than education focusing on vitamin supplementation.

Beneficial effects of topical anti-inflammatory drugs against sulfur mustard-induced ocular lesions in rabbits.

Ocular injuries following sulfur mustard (HD) exposure are characterized by an inflammatory response, observed as eyelid swelling, conjunctivitis, corneal oedema and cellular infiltration starting 1-4 h after exposure, depending on dose. These effects heal partially during the first 1-2 weeks after exposure, with the later appearance of neovascularization, recurrent erosions and recurrent oedema of the cornea (delayed response). We have shown previously that topically applied steroid treatment, administered after HD exposure, attenuated the extent of neovascularization, one of the characteristics of delayed ocular pathology in rabbits. The present study was designed to characterize further the initial inflammatory response and to elucidate the role of anti-inflammatory (AI) drugs as a potential therapy. Rabbit eyes were exposed to HD vapour (390 microg l(-1) for 2 min) and were treated with a topical commercial ophthalmic solution of dexamethasone or diclofenac, starting 1 h post-exposure (four times a day). Inflammation was evaluated by clinical observations, biochemical analysis of aqueous humour and by histology. Sulfur mustard exposure initiated typical clinical ocular symptoms within 4-6 h after exposure. Biochemical analysis of aqueous humour showed that protein content and prostaglandin E (PGE) increased significantly at 6 h and were still high 48 h after HD exposure. Light microscopy evaluation revealed severe damage to the cornea, characterized by epithelial denudation, oedema and cellular infiltration (mostly eosinophiles) in the stroma. Both treatments were effective in alleviating the clinical symptoms and in preventing the HD-induced increase in protein and PGE in the anterior chamber, as well as the cellular infiltration, in the corneal stroma. However, the AI treatments had no therapeutic effect on corneal erosions, and a short delay in epithelial regeneration was noted. It is concluded that AI drugs are potential candidates for the treatment of ocular lesions following HD exposure.

Prevention and management of omental herniation after laparoscopy.

Omental herniation through laparoscopic cannula sites is an uncommon but serious complication of laparoscopy. Its frequency will probably increase as more and different types of endoscopic surgery are performed. Omental herniation occurred in two women and was corrected under local anesthesia.

Enabling conception and pregnancy. Midwifery care of women experiencing infertility.

This article provides a comprehensive and thoughtful overview of primary midwifery care of the woman experiencing infertility. Midwifery assessment and management strategies that can assist women and their partners experiencing infertility to achieve a successful pregnancy are reviewed. In addition to physiologic considerations, the article addresses psychosocial, spiritual, legal, and financial issues essential to understanding the ramifications of infertility care. The authors frame their approach in a feminist perspective that enables the woman to achieve control of fertility and self-determination of care.

Predicting probabilities of pregnancy and multiple gestation from in vitro fertilization--a new model.

OBJECTIVE: To develop a statistical model that adjusts for variation between patients and adequately predicts the observed distribution of pregnancies among singletons and multiple gestations of various orders. METHODS: All in vitro fertilization (IVF) cycles from the inception of the IVF program at Women and Infants' Hospital on May 26, 1988, until December 31, 1993, were evaluated using logistic regression in selected subsets. RESULTS: A new cycle-one specific model uses three different probabilities: P1, the probability of pregnancy (predicted by age and total embryo score); P2/P1, the conditional probability of finding a second implantation in those who had become pregnant with at least one (predicted by total embryo score); and P3/P2, the conditional probability of finding a third implantation in those who had become pregnant with at least two (with no significant predictors). This is the first model to use these three adjusted probabilities. CONCLUSION: P1 increases with increasing total embryo score but decreases with increasing age. P2/P1 increases with increasing total embryo score but does not depend on age. Embryo scoring is useful because the total embryo score is a better predictor of P1 and P2/P1 than the number of embryos alone. By using patient-specific information (age and total embryo score) and cycle-specific tables, an estimate of the probability of pregnancy and multiple gestation can be provided before embryo transfer.

Closure of Pfannenstiel skin incisions. Staples vs. subcuticular suture.

OBJECTIVE: To compare skin closure with staples and subcuticular suture. STUDY DESIGN: Obstetric patients undergoing cesarean section with a Pfannenstiel incision were prospectively randomized to skin closure with staples or subcuticular suture. Pain and cosmesis were assessed postoperatively. RESULTS: Patients reported significantly less pain following subcuticular closure at both the time of discharge (P < or = .01) and the postoperative visit (P < or = .002). Incisions closed with subcuticular suture were found to be more cosmetically attractive by both patients (P = .04) and physicians (P = .01) at the postoperative visit. CONCLUSION: Pfannenstiel skin incisions closed with subcuticular closure following cesarean section result in less postoperative discomfort and are more cosmetically appealing at the six-week postoperative visit as compared to incisions closed with staples.

Serum triple-marker screening in in vitro fertilization and naturally conceived pregnancies.

OBJECTIVE: To determine whether results of second-trimester maternal serum triple-marker screening for Down syndrome and open neural tube defects in singleton pregnancies conceived from in vitro fertilization (IVF) differ from those of pregnancies conceived spontaneously. METHODS: The screen-positive rates and triple-marker levels of patients conceiving singleton pregnancies by IVF were compared to age-adjusted standards. RESULTS: Sixty-nine singleton IVF pregnancies with maternal serum screening were identified. Twenty-one (30.4%) of the 69 IVF singleton pregnancies had a positive screen for Down syndrome compared with a 14.4% expected screen-positive rate for the maternal age distribution in our observed sample (P = .013). The screen-positive rate for open neural tube defects in the measured population was similar to anticipated values based on historic controls (5.8% in IVF patients versus 5.3% in the total population). The median levels of the triple markers were 0.95 multiples of the median (MoM) for alpha-fetoprotein (AFP), 0.90 MoM for unconjugated estriol (E3), and 1.22 MoM for hCG. CONCLUSION: The increased hCG levels as well as the slightly lower AFP and unconjugated E3 levels may contribute to the higher Down syndrome screen-positive rate in this IVF singleton population. These results may be due to the number of embryos transferred, the maternal hormonal environment of the IVF process, or other factors. Pregnancies conceived by IVF may be twice as likely to have a positive maternal serum screening test. As additional data are collected, corrected standards should be determined.

The impact of hydrosalpinx on successful pregnancy in tubal factor infertility treated by in vitro fertilization.

OBJECTIVE: To determine the impact of hydrosalpinx on pregnancy rates in patients undergoing IVF for infertility caused by tubal disease. DESIGN: Review of the records of all patients who had undergone IVF for tubal factor infertility at our institution between May 1988 and October 1994. SETTING: A university-sponsored, hospital-based IVF facility. PATIENT(S): Two hundred fifty patients were identified with infertility due to tubal disease; 67 of these had at least one documented hydrosalpinx whereas the remaining 183 did not. MAIN OUTCOME MEASURE(S): Numbers of oocytes retrieved and fertilized, the number of embryos transferred and implanting, and resulting pregnancy rates. RESULT(S): The groups were similar in age and cycle cancellation rates. The patients with hydrosalpinx had greater numbers of oocytes retrieved per cycle (15.0 versus 11.6) and embryos transferred per cycle then those without hydrosalpinges (4.21 versus 3.98). The hydrosalpinx group also undertook more cycles per patient (2.31 versus 1.96). Fertilization rates between the two groups were similar, but implantation rates were decreased in those with hydrosalpinx (8.5% versus 11.2%). CONCLUSION(S): Hydrosalpinx did not result in impaired ovarian stimulation or decreased oocyte fertilization. It did, however, interfere with implantation and reduce to some degree the success of IVF in achieving an ongoing pregnancy. The validity of routine salpingectomy for hydrosalpinx is debatable, but its use in selected individuals may well be appropriate.

Effects of fetal number and multifetal reduction on length of in vitro fertilization pregnancies.

OBJECTIVE: To determine the effects of multifetal reduction and other variables on the duration of gestation of in vitro fertilization (IVF) pregnancies. METHODS: All 274 IVF pregnancies from the inception of the Women and Infants' Hospital IVF Program on May 26, 1988, until December 31, 1993, were evaluated. RESULTS: Spontaneous reduction occurred in ten pregnancies, and multifetal reduction was elected in 28 multiple gestations. Among 260 pregnancies that remained viable beyond 20 weeks, 162 singletons (37.9 +/- 0.29 weeks; mean +/- standard error) had a longer mean gestation than did 64 twins (34.6 +/- 0.61 weeks), 25 pregnancies reduced to twins (33.4 +/- 1.0 weeks), or nine triplets (29.7 +/- 1.9 weeks). Triplets delivered 4.9 weeks earlier than nonreduced twins (P < .05) and 3.7 weeks before twins resulting from multifetal pregnancy reduction (P < .05). Regression analysis showed that at the 8-week ultrasound, each viable fetus could be expected to reduce the duration of the gestation by about 3.6 weeks, and each fetus reduced medically or as a result of natural causes could be expected to prolong the gestation by approximately 3.0 weeks. Only 14% of triplet pregnancies underwent spontaneous multifetal reduction. CONCLUSION: Multifetal reduction of pregnancies with three or more fetuses was beneficial and increased the duration of gestation.

Serum inhibin levels are lower in ectopic than intrauterine spontaneously conceived pregnancies.

OBJECTIVE: To determine if serum inhibin concentrations are lower in ectopic (EP) versus intrauterine pregnancies (IUPs) that are conceived spontaneously. DESIGN: Case-control study. SETTING: Academic clinical practice. PATIENTS: Serum samples were obtained from 19 women who had EP confirmed at surgery and by pathology. For comparison, serum samples were collected from 24 women of similar chronological and gestational age with sonographic evidence of an IUP. MAIN OUTCOME MEASURE: Serum dimeric inhibin-A, total inhibin, P, and hCG. RESULTS: Serum total and dimeric inhibin concentrations in women with EP were < 60% of the concentrations for women with single IUPs. Total inhibin, but not dimeric inhibin-A, was elevated in maternal serum before week 8 of gestation relative to normal menstrual cycle levels. CONCLUSIONS: Serum inhibin concentrations are lower in EP as compared with IUPs that are spontaneously conceived and the relative amounts of dimeric inhibin-A, B, and alpha inhibin subunit in maternal serum may change throughout gestation.

Relaxin secretion in in vitro fertilization pregnancies.

OBJECTIVE: This study was designed to determine whether the late luteal functional status of the corpora lutea in in vitro fertilization cycles alters the secretion of relaxin during pregnancy. STUDY DESIGN: Analysis of serum relaxin, human chorionic gonadotropin, and steroid concentrations in sera of women with pregnancies viable beyond the twelfth week as a result of in vitro fertilization treatment was performed. RESULTS: The serum estradiol and progesterone concentrations decreased 5.5- and 4-fold from days 5 to 6 after human chorionic gonadotropin to days 11 to 13 after human chorionic gonadotropin, respectively. The serum relaxin concentration increased 8-fold between the 11- to 15-day interval and the 16- to 50-day interval after human chorionic gonadotropin and another 6-fold to the 51- to 90-day interval after human chorionic gonadotropin (all p < 0.01). Multiple linear regression analysis showed that the serum estradiol level 11 to 13 days after human chorionic gonadotropin and the serum human chorionic gonadotropin level 11 to 15 days after human chorionic gonadotropin were the most powerful paired predictors of the concentration of serum relaxin measured in the 11- to 15-day interval after human chorionic gonadotropin interval (R2 = 0.39, n = 50), the 16- to 50-day interval (R2 = 0.61, n = 51), and the 51- to 90-day interval (R2 = 0.55, n = 39). CONCLUSION: Secretion of relaxin is determined by an interaction of the late luteal functional status of the corpora lutea and the human chorionic gonadotropin secreted by the implanting pregnancy. These data allow for the hypothesis that inducing functional luteolysis by substituting one or more injections of luteinizing hormone for the human chorionic gonadotropin injection may decrease secretion of steroids, relaxin, and other factors from the corpora lutea during pregnancy, decreasing the risk of premature delivery in multiple gestations and the ovarian hyperstimulation syndrome.

Laparoscopic-assisted tubal anastomosis.

STUDY OBJECTIVE: To determine the length of procedure, length of hospital stay, complications, and postoperative pregnancy rates of traditional tubal anastomosis (TA) and laparoscopic-assisted TA (LATA). DESIGN: A comparison of 8 women undergoing LATA with 11 patients operated on by the same surgeon during a similar time period who were not candidates for, or did not desire, a laparoscopic approach. SETTING: Academic practice tertiary care setting. PATIENTS: Women requesting reversal of tubal ligation. INTERVENTIONS: Tubal anastomosis by laparoscopy or laparotomy. MEASUREMENTS AND MAIN RESULTS: Patients undergoing the two procedures did not differ by age or parity, although those selected for LATA had a lower body mass index (23.2 +/- 1.4 vs 30.8 +/- 2.0 kg/m2, p = 0.01). Although the LATA took longer (251 +/- 14 vs 194 +/- 10 min, p = 0.004), hospital stay was significantly shorter than for traditional TA (1.8 +/- 0.3 vs 3.0 +/- 0.1 days, p = 0.004). Of the eight LATAs, six were completed and two were converted to laparotomy. For all patients with follow-up, clinical pregnancy rates were 43% and 29% (NS) for TA and LATA, respectively, with 100% of the former and 80% (NS) of the latter group who did not conceive having at least one patent tube on hysterosalpingogram. CONCLUSIONS: Laparoscopic-assisted TA is a possible alternative to the traditional TA performed by laparotomy. Ideal candidates for LATA appear to be women without obesity and with proximal tubal segments of 3 cm or greater. Larger studies with longer follow-up will define appropriate candidates and identify long-term results.

Efficacy of oral micronized progesterone in the treatment of luteal phase defects.

OBJECTIVE: Vaginal progesterone suppositories are an accepted treatment for infertility attributed to luteal phase defects. Although oral micronized progesterone may be preferable to suppositories for many patients, there are no studies on its use for patients with luteal phase defects. This study evaluated the efficacy of oral micronized progesterone for the treatment of luteal phase defects. STUDY DESIGN: Seven women with luteal phase defects previously corrected by vaginal suppositories were administered oral micronized progesterone (200 mg by mouth three times a day). Endometrial biopsies were performed to evaluate treatment efficacy. Questionnaires were used to assess side effects, including sedation. RESULTS: On oral micronized progesterone, all patients had in-phase endometrial biopsies. Despite complaints of drowsiness, the majority of patients preferred the oral formulation over the vaginal route of administration. CONCLUSION: We conclude that oral micronized progesterone is efficacious in the treatment of luteal phase defects.

The hot flash: pathophysiology and treatment.

Hot flashes are the most frequent somatic complaint of women going through the menopause. Although the exact pathophysiology of the hot flash remains unknown, it appears to be related to an alteration in the set point of the hypothalamic thermoregulatory center. With the withdrawal of estrogen, some event parallel to the release of GnRH (and subsequent release of LH) causes a decrease in the set point of the thermoregulatory center. The hot flash, with its characteristic sweating and vasodilation, represents the attempt to decrease the body core temperature and restore equilibrium. Estrogen therapy reliably treats hot flashes in the majority of women in addition to its proven beneficial effect on heart disease and osteoporosis. It is rare that health care providers can so reliably and safely positively impact on a patient's symptoms and overall health.