Association between oocyte retrieval technique and number of oocytes retrieved.

PURPOSE: To assess if there is an optimal oocyte retrieval (OR) technique to retrieve a maximum number of oocytes and mature oocytes (MII). METHODS: Retrospective cohort study in which nine physicians completed a survey on OR techniques. Number of oocytes/follicle cohort, MIIs/follicle cohort, and MIIs/oocytes retrieved (%MII) were assessed for each technique for patients undergoing OR from 3/2013 to 7/2019. Data were stratified by number of follicles on ultrasound on day of trigger (< 6, 6-10, > 10). RESULTS: Patient demographics were equivalent between techniques. For < 6 follicles, three techniques resulted in significantly fewer oocyte/follicle (0.97 ± 0.48, 0.95 ± 0.66, and 0.90 ± 0.41) compared to the top-performing technique (TPT) (1.11 ± 0.55). For 6-10 follicles, two techniques resulted in significantly fewer oocyte/follicle (0.95 ± 0.39 and 0.93 ± 0.35) compared to the TPT (1.06 ± 0.42). A different technique had higher %MII (0.77 ± 0.19) compared to two techniques (0.74 ± 0.21 and 0.72 ± 0.22). For > 10 follicles, two techniques resulted in significantly fewer oocyte/follicle (1.01 ± 0.42 and 1.07 ± 0.40) compared to the TPT (1.15 ± 0.41). These two techniques also resulted in fewer MII/follicle (0.75 ± 0.33 and 0.81 ± 0.34 vs. 0.87 ± 0.34). There was no consistent TPT across follicle number groups or for all outcome variables. CONCLUSIONS: There does not appear to be a clear TPT, even for patients with few follicles. Providers who perform OR in a similar fashion to physicians at our institution should feel confident that those techniques obtain equivalent oocyte yields.

Embryo attrition in planned PGT-A: predicting the number of available blastocysts for transfer.

PURPOSE: During a typical IVF cycle, there is unavoidable attrition from oocytes retrieved to blastocysts formed. Some patients will not have blastocysts available to biopsy or embryos for transfer. The purpose of this study was to predict the number of transferable blastocysts available for patients based on their age and number of 2pn zygotes. METHODS: This was a retrospective cohort study of all fresh autologous IVF and ICSI cycles in which PGT-A was planned from 1/2012 to 3/2020. In total, 746 cycles from 571 patients were analyzed. Patient cycles were stratified into two groups: less than four 2pn zygotes (n = 85) and at least four 2pn zygotes (n = 661). Cycles were then stratified by patient age. Cycle outcomes, including number of cleavage-stage embryos, blastocysts, euploid blastocysts, and low level mosaic blastocysts, were determined. RESULTS: Cleavage-rate was independent of age and number of 2pn zygotes and ranged between 96 and 100%. Blastocyst conversion and euploid blastocyst conversion rates were directly correlated to age, ranging from 52 to 83% for blastocyst conversion and 0-28% for euploid blastocyst conversion. For patients above the age of 40 years with less than four 2pn zygotes, the risk of having no transferable embryos was 99.7%. CONCLUSION: While the literature demonstrates higher live birth rates with the use of PGT-A in women of advancing age, this is inconsequential if there is no embryo available to transfer. Women over 40 years with less than four 2pn zygotes should consider transfer of one or more untested embryos either on day 3 or on day 5.

Blastocyst conversion rate and ploidy in patients with structural rearrangements.

OBJECTIVE: The primary objective of this study was to test the hypotheses that compared to IVF cycles undergoing preimplantation genetic testing for aneuploidy (PGT-A) with or without testing for monogenic disorders (PGT-M), IVF cycles undergoing PGT for structural rearrangements (PGT-SR) will have (1) a poorer blastocyst conversion rate and (2) fewer usable blastocysts available for transfer. Secondarily, the study aimed to compare pregnancy outcomes among PGT groups. PATIENTS: Retrospective cohort study including cycles started from January 1, 2012, to March 30, 2020, with the intent of pursuing PGT-A, PGT-A with PGT-M, and PGT-SR, with trophectoderm biopsy on days 5 or 6. RESULTS: A total of 658 women underwent 902 cycles, including 607 PGT-A, 216 PGT-A&M, and 79 PGT-SR cycles. When compared with the blastocyst conversion rate for the PGT-A group (59.4%), and after adjustment for patient age, total number of mature oocytes, BMI, and ICSI, there were no significant differences for either the PGT-A&M (69.7%, aRR 1.03, 95% CI 0.96-1.10) or PGT-SR (63.2%, aRR1.04, 95% CI 0.96-1.13) groups. Compared to the PGT-A group, the proportion of usable blastocysts was statistically significantly lower in the PGT-SR group: 35.1% versus 24.4% (aRR 0.57, 95% CI 0.46-0.71) and the PGT-A&M group: 35.1% versus 31.5% (aRR 0.68, 95% CI 0.58-0.81). Implantation, pregnancy, and miscarriage rates were equivalent for all groups. CONCLUSION: Patients with structural rearrangements have similar blastocyst development but significantly fewer usable blastocysts available for transfer compared to PGT-A testers. Nevertheless, with the transfer of a usable embryo, PGT-SR testers perform as well as those testing for PGT-A.

Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function.

BACKGROUND: The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. METHODS: All subjects were menstruating women <42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n = 535). Control subjects (n = 521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. RESULTS: The frequency of the premutation (7/535 versus 1/521; P< 0.05) and intermediate alleles (17/535 versus 7/521; P< 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 ± 7.1 versus 31.6 ± 4.3; P < 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 ± 0.02 (P < 0.01). A repeat cutoff of 45 had a specificity of 98%, but a sensitivity of only 5% to identify occult POI. The positive predictive value was only 21% for a fertility population that has ∼ 22% of its patients with occult POI. CONCLUSIONS: The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.

Msx2 induces epithelial-mesenchymal transition in mouse mammary epithelial cells through upregulation of Cripto-1.

Epithelial-mesenchymal transition (EMT) is a process occurring during both embryogenesis and early stages of invasive cancer. Epithelial cells that undergo EMT become more migratory and invasive with a mesenchymal morphology. Herein we assess EMT induction in a mouse mammary epithelial cell line driven by Msx2, a homeobox-containing transcription factor important during mammary gland development. NMuMG cells, a normal mouse mammary epithelial cell line, stably transfected with a Msx2 cDNA showed downregulation of an epithelial marker E-cadherin and upregulation of the mesenchymal markers vimentin and N-cadherin. Furthermore, overexpression of Cripto-1, a member of the epidermal growth factor-CFC protein family already known to be involved in EMT, was detected in Msx2-transfected cells. The expression of Cripto-1 was accompanied by activation of the tyrosine kinase c-Src pathway and an increase in the invasive ability of the cells. Functional assays also demonstrated inhibition of the invasive behavior of the Msx2-transfected cells by a c-Src specific inhibitor. Moreover, immunohistochemistry of human infiltrating breast carcinomas showed positive staining for Msx2 only in the infiltrating tumor cells while the non-infiltrating tumor cells were negative. These results suggest that Msx2 may play a significant role in promoting EMT in epithelial cells that acquire properties involved in tumor invasion. J. Cell. Physiol. 219: 659-666, 2009. Published 2009 Wiley-Liss, Inc.

Thin Films of n-Si/Poly-(CH3)3Si-Cyclooctatetraene: Conducting-Polymer Solar Cells and Layered Structures.

The optical and electronic properties of thin films of the solution-processible polymer poly-(CH(3))(3)Si-cyclooctatetraene are presented. This conjugated polymer is based on a polyacetylene backbone with (CH(3))(3)Si side groups. Thin transparent films have been cast onto n-doped silicon (n-Si) substrates and doped with iodine to form surfacebarrier solar cells. The devices produce photovoltages that are at the theoretical limit and that are much greater than can be obtained from n-Si contacts with conventional metals. Two methods for forming layered polymeric materials, one involving the spincoating of preformed polymers and the other comprising the sequential polymerization of different monomers, are also described. An organic polymer analog of a metal/insulator/metal capacitor has been constructed with the latter method.

Interlobular and intralobular mammary stroma: genotype may not reflect phenotype.

BACKGROUND: The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes. METHODS: Fresh normal breast tissue was collected from reduction mammoplasty patients and immediately placed into embedding medium and frozen on dry ice. Tissue sections were subjected to laser capture microscopy to isolate the interlobular from the intralobular fibroblasts. RNA was prepared and subjected to microarray analysis using the Affymetrix Human Genome U133 GeneChip. Data was analyzed using the Affy and Limma packages available from Bioconductor. Findings from the microarray analysis were validated by RT-PCR and immunohistochemistry. RESULTS: No statistically significant difference was detected between the gene expression profiles of the interlobular and intralobular fibroblasts by microarray analysis and RT-PCR. However, for some of the genes tested, the protein expression patterns between the two subtypes of fibroblasts were significantly different. CONCLUSION: This study is the first to report the gene expression profiles of the two distinct fibroblast populations within the human mammary gland. While there was no significant difference in the gene expression profiles between the groups, there was an obvious difference in the expression pattern of several proteins tested. This report also highlights the importance of studying gene regulation at both the transcriptional and post-translational level.

Responses to fertility treatment among patients with cancer: a retrospective cohort study.

BACKGROUND: Cancer treatments have significant negative impacts on female fertility, but the impact of cancer itself on fertility remains to be clarified. While some studies have shown that compared with healthy women, those with cancer require higher doses of gonadotropins resulting in decreased oocyte yields, others have shown comparable oocyte yields between the two groups. The purpose of this study is to evaluate whether there is an association between any cancer and/or type of cancer, and response to ovarian stimulation for egg and embryo banking. METHODS: In this retrospective cohort study, ovarian stimulation cycles performed from June 2007 through October 2014 at a single academic medical center were reviewed to identify those undertaken for women with cancer undergoing fertility preservation (n = 147) or women with no cancer undergoing their first cycle due to male factor infertility (n = 664). Of the 147 women undergoing fertility preservation, 105 had local cancer (Stage I-III solid malignancies) and 42 had systemic cancer (hematologic or Stage IV solid malignancies). Response to ovarian stimulation was compared among these two groups and women with no cancer. RESULTS: Adjusting for age and BMI, women with systemic cancer had lower baseline antral follicle counts (AFC) than women with no cancer or local cancer. Women with systemic cancer required higher doses of FSH than women with no cancer or local cancer, and they had higher oocyte to AFC ratios than women with no cancer or local cancer, but greater odds of cycle cancellation as compared to women with no cancer or local cancer. No significant differences were observed among the three groups for duration of stimulation, number of oocytes and mature oocytes retrieved, or number of embryos created. CONCLUSIONS: Women with cancer achieve similar oocyte and embryo yields as women with no cancer, although those with systemic cancer require higher FSH doses and are at greater risk of cycle cancellation.

Are women with obesity and infertility willing to attempt weight loss prior to fertility treatment?

OBJECTIVE: To assess attitudes towards weight loss interventions in patients seeking infertility treatment. METHODS: We evaluated prior weight loss experiences, attitudes towards future interventions by body mass index (BMI), and willingness to delay fertility treatment for weight loss interventions stratified by BMI using logistic regression amongst women ≤45years old with infertility over three months or recurrent pregnancy loss. RESULTS: The average age of our convenience sample of respondents (148 of 794 eligible women, 19%) was 34.5 years old, with a mean BMI of 26.7±7.4kg/m2, including 37 with a BMI >30kg/m2 (25%). Most women had attempted conception over 1year. The majority of women with overweight or obesity were attempting weight loss at the time of survey completion (69%). While 47% of these women reported interest in a supervised medical weight loss program, 92% of overweight women and 84% of women with obesity were not willing to delay fertility treatment more than 3 months to attempt weight loss. CONCLUSION: Most women with obesity and infertility in our population are unwilling to postpone fertility treatment for weight loss interventions.

Prolactin synthesis and secretion by human breast cancer cells.

A possible autocrine function of prolactin (Prl) in human breast cancer was explored by the addition of a panel of anti-human Prl mAbs to T47Dco and MCF7 human breast adenocarcinoma cells. mAb 631 and mAb 390 inhibited cell growth by 86 and 68%, respectively, in the estrogen receptor-negative T47Dco cells and by 20 and 71%, respectively, in the estrogen receptor-positive MCF7 cells. Conditioned medium prepared from T47Dco cells was assessed for the presence of Prl-like molecules by its ability to stimulate growth of Prl-responsive Nb2 rat lymphoma cells. Growth of Nb2 cells under the influence of human Prl or conditioned medium was abolished when either solution was pretreated with mAb 390, followed by Immunobead precipitation (Bio-Rad, Melville, NY). T47Dco cells secrete 0.7 microgram lactogen/ml over a 24-48-h period. With the use of reverse transcription-PCR, an expected 612-bp band was detected by ethidium bromide staining, and its similarity to pituitary Prl was confirmed by Southern blot analysis with the use of human Prl cDNA as a probe. A single M(r) 22,000 band, the dominant size of monomeric pituitary Prl, was found in immunoprecipitates of both cell extracts and conditioned medium from T47Dco cells labeled metabolically with [35S]cysteine. These data suggest that human breast cancer cells synthesize and secrete biologically active Prl.

Pregnancy outcomes in in vitro fertilization cycles with serum estradiol drop prior to human chorionic gonadotropin.

OBJECTIVE: To study the effect of an unpredictable drop in serum estradiol prior to hCG administration on pregnancy outcomes in in vitro fertilization cycles. METHODS: 3653 consecutive IVF cycles from January 1, 1998 to December 31, 2000 at Brigham and Women's Hospital were reviewed, and 65 cycles in which oocyte retrieval (ER) was performed following a drop in serum estradiol (E(2)) not associated with intentional withdrawal of gonadotropins were identified. Daily gonadotropin dose was decreased at some time in 25 of these cycles, while the remaining 40 cycles did not have a reduction in gonadotropin dose. A retrospective case-control study of the respective live birth rates and pregnancy loss rates of patients with unpredictable E(2) drops in the 65 study cycles were compared to 65 age matched controls. RESULTS: Live birth rates (32% vs. 35%, p=0.72) and pregnancy loss rates (28% vs. 30%, p=0.76) were similar for all study and control groups respectively. There were no differences in live birth and pregnancy loss rates in cycles undergoing gonadotropin dose reduction (40% vs. 44%, p=0.78 and 29% vs. 39%, p=0.70) and cycles without gonadotropin dose reduction (28% vs. 30%, p=0.81 and 27% vs. 20%, p=0.72). CONCLUSIONS: In the absence of coasting, a drop in serum estradiol levels during GnRH-agonist downregulated controlled ovarian hyperstimulation for IVF prior to hCG is not associated with a decrease in live birth rates or pregnancy loss rates.

Estrogen absorption and metabolism in postmenopausal women with end-stage renal disease.

Women with end-stage renal disease (ESRD) have a higher rate of death from heart disease than women with normal renal function. Because estrogen replacement therapy may significantly decrease the incidence of death due to cardiovascular disease in postmenopausal women with normal renal function, their use has been considered for women with ESRD. However, the pharmacokinetics of estrogen have not been studied in postmenopausal women with ESRD to determine the optimal estrogen dose. Six postmenopausal women with ESRD receiving maintenance hemodialysis and six controls matched for body mass index were admitted to the in-patient Clinical Research Center. A 1- or 2-mg oral estradiol (E2) pill was given while subjects fasted. Blood sampling was performed over the next 24 h for measurement of E2, estrone (E1), albumin, and sex hormone-binding globulin (SHBG). Three weeks later, the subjects were given the other E2 dose under identical conditions. At baseline, total and free E2 levels were higher in the subjects with ESRD than in controls (P = 0.0005 and 0.0035, respectively). After ingestion of 1 and 2 mg E2, total and free E2 levels remained significantly higher in the ESRD subjects from 2-8 h after treatment (P < or = 0.05). After 1 mg oral E2, total serum E2 peaked at 65 pg/mL at 4 h in ESRD subjects and at 27 pg/mL in control subjects at 8 h. After 2 mg oral E2 treatment, total serum E2 peaked at 8 h in both ESRD and control subjects, with levels of 99 and 37 pg/mL, respectively. E1 was higher in the subjects with ESRD than in the control subjects at baseline (P < 0.05). After ingestion of 1 mg E2, E1 concentrations were not significantly higher in ESRD than in control subjects, peaking at 180 and 121 pg/mL, respectively (P = 0.3). E1 concentrations were higher in ESRD than in control subjects after the ingestion of 2 mg E2, with peak levels of 376 and 201 pg/mL, respectively (P = 0.03). Total and free E2 levels are higher in patients with ESRD than in control subjects at baseline and after E2 ingestion, indicating that renal failure alters the pharmacokinetics of both endogenous and exogenous E2. Therefore, conventional E2 doses used in individuals with normal renal function may be excessive for patients with ESRD.

The regulation of mammary prolactin receptor metabolism by a retroviral envelope protein.

In a previous study, infection with the mouse mammary tumor virus (MMTV) was shown to increase the sensitivity of the mammary epithelium toward prolactin (PRL); furthermore, this effect could be mimicked by the binding of the MMTV envelope protein (gp52) to its cell receptor. The present work has investigated the possibility that gp52-induced changes in the PRL receptor (PRLR) were responsible for this phenomenon. In vitro, gp52 doubled the PRLR concentration in the plasmalemma of mammary epithelium without affecting the affinity. The origins of these PRLRs were twofold: first, gp52 stimulated PRLR mRNA nearly fivefold, suggesting that some of the receptors were newly synthesized. Second, there was a redistribution of PRLRs within the mammary cell: PRLRs were shifted from an internal pool to the plasma membrane. This relocation was very rapid, occurring within 30 min. There did not appear to be any contribution from alterations in PRLR degradation, since the half-life of PRLR was not affected by gp52. In summary, the MMTV increases the PRL sensitivity of mouse mammary epithelium by elevating PRLRs through both enhanced synthesis and recruitment from microsomes.

Epidermal growth factor stimulates the growth of A431 tumors in athymic mice.

Growth of the human epidermoid carcinoma cell line A431 in vitro is stimulated by low concentrations of epidermal growth factor (EGF; 0.1-10 pM) and inhibited by high concentrations (0.1-10 nM). This cell also grows as a solid tumor in female athymic mice. Sustained high levels of EGF in vivo can be achieved by the administration of testosterone to female mice via a cholesterol-based pellet inserted subcutaneously. This chronic elevation of EGF levels (serum concentration = 90 ng/ml), however, does not affect growth of the tumor. In contrast, low levels of the growth factor (0.5 micrograms/g body wt by injection 5 times/week; serum concentration = 8.25 ng/ml) stimulate growth of the tumor. These data suggest that the mechanism(s) involved in the inhibition of A431 cell growth by EGF in vitro does not function in vivo and the physiologically significant effect of EGF in vivo is growth promotion.

Stimulation of growth of human breast cancer cells (T47D) by platelet derived growth factor.

The human breast cancer cell lines T47D and MCF-7, respond to the mitogenic action of exogenously added PDGF with a 2-3-fold increase in cell number. The maximal response was obtained at a concentration of 1.25 half maximal units/ml (125 ng/ml). PDGF-AA was even more effective than PDGF-AB while PDGF-BB was without effect. The growth-enhancing activity of PDGF was completely abolished by Fab fragments of anti PDGF. Within 7 min of addition of PDGF to cultures of T47D cells, specific phosphorylation of a 65-kDa protein was observed. T47D cells contain specific receptors for PDGF with approximately 4-7 x 10(4) sites (kDa of 3-4 x 10(-10) M) per cell.

Progesterone induces side-branching of the ductal epithelium in the mammary glands of peripubertal mice.

Development of the functional secretory epithelium in the mammary gland of the female mouse requires the elongation of the anlage through the mammary fat pad to form the primary/secondary ductal network from which tertiary ductal side-branches and lobuloalveoli develop. In this study we examined the hormonal requirements for the spatial development of the primary/secondary epithelial network and tertiary side-branches by quantifying ductal growth and epithelial cell proliferation in normal and hormone-treated BALB/c mice between 21 and 39 days of age. In normal mice, an allometric increase in ductal length commenced at 31 days of age and resulted in completion of the primary/secondary ductal network by 39 days of age. Concurrent with this allometric growth was a significant increase in cellular proliferation in the terminal end-buds (TEBs) of the ductal epithelium from 29 days of age, as determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation. A level of cellular proliferation similar to that in the TEBs of 33-day-old control mice could be induced in the TEBs of 25-day-old mice following treatment for 1 day with estrogen (E), or progesterone (P) or both (E/P), indicating that both E and P were mitogenic for epithelial cells of the peripubertal TEBs. However, the period of allometric ductal growth in untreated mice did not correspond to an increase in serum E or P (which might have been expected during the estrous cycle). In addition, epithelial growth was not observed in mammary glands from 24-day-old mice that were cultured in vitro with E, P or E/P. In contrast to treatment with E, treatment with P promoted a dramatic increase, relative to control mice, in the number of tertiary branch points upon the primary/secondary ductal network. BrdU labeling of mammary glands from 24- 33-day-old mice pelleted with cholesterol (C), E, P or E/P confirmed the greater mitogenicity of P on the epithelial cells of the secondary/tertiary ducts as compared with C or E. Concurrent with these changes, localized progesterone receptor (PR) expression in clusters of cells in the ductal epithelium was associated with structures that histologically resembled early branch points from ductules. In conclusion, our results suggest that additional endocrine growth factor(s) other than E and P contribute to the development of the primary/secondary ductal network, and that P is responsible for the formation of tertiary side-branches in the mammary glands of mice during puberty.

Studies on the in vitro interaction of mitomycin C, nitrofurantoin and paraquat with pulmonary microsomes. Stimulation of reactive oxygen-dependent lipid peroxidation.

In vitro experiments were performed to evaluate the capacity of the redox cycling compounds mitomycin C (MC), nitrofurantoin (NF) and paraquat (PQ) to stimulate pulmonary microsomal lipid peroxidation. It was observed that the interaction of MC, NF or PQ with rat or mouse lung microsomes in the presence of an NADPH-generating system and an O2 atmosphere resulted in significant lipid peroxidation. All three compounds demonstrated similar concentration dependency, similar time courses and the ability to generate lipid peroxidation-associated chemiluminescence. The stimulation of lipid peroxidation by MC, NF or PQ was inhibited significantly by superoxide dismutase, glutathione, ascorbic acid, catalase and EDTA, agents which either scavenge reactive oxygen and/or prevent the generation of secondary reactive oxygen metabolites. In addition, the ability of MC or NF, but not PQ, to stimulate lipid peroxidation was reduced significantly following preincubation with microsomes and NADPH under N2 (15-20 min) prior to incubation under O2. During this period under N2. MC and NF underwent reductive metabolism of their quinone and nitro moieties respectively. Thus, it appears that under aerobic conditions the pulmonary microsomal-mediated redox cycling of MC, NF and PQ is accompanied by the stimulation of reactive oxygen-dependent lipid peroxidation.

Estrogen, alcohol and breast cancer risk.

Estrogen replacement has been used for many years to reverse the hypoestrogenic symptoms of menopause and prevent osteoporosis. Studies have found that estrogen replacement also decreases cardiovascular risk. In addition, social use of alcohol has been found to decrease cardiovascular risk. Therefore, both estrogen replacement therapy and alcohol use have been proposed to have cardiovascular benefits, and are often used in combination. Epidemiologic evidence indicates that estrogen replacement therapy after menopause increases breast cancer risk. Regular alcohol consumption is also associated with increase in risk. However, interactions between the two are poorly understood. In addition, if alcohol alters circulating estrogen levels in estrogen users, this may have implications in terms of altering the risks:benefit ratio of estrogen replacement in an undesirable direction. For example, there are data suggesting that the use of both alcohol and estrogen may increase breast cancer risk more than the use of either one alone. Data support both acute and chronic effects of alcohol in raising circulating estrogen levels in premenopausal women on no hormonal medications. In postmenopausal women studies focusing on acute effects of alcohol on estrogen metabolism indicate that alcohol has a much more pronounced effect in women using estrogen replacement than in those who do not. Studies evaluating chronic effects of alcohol ingestion on circulating estrogens in postmenopausal women are needed.

Predicting risk of complications with gynecologic laparoscopic surgery.

OBJECTIVE: To determine the incidence and predictors of risk for operative complications, conversions to laparotomy, and postoperative admissions after laparoscopic procedures. METHODS: We obtained demographic information on and medical histories of a consecutive series of 843 women who underwent laparoscopic surgery for all procedures other than tubal ligation at Brigham and Women's Hospital during 1994. All major complications after surgery were recorded. Major operative complications were defined as bowel, bladder, ureter, or vascular injuries or significant abdominal wall or other internal bleeding. Categorical analysis was used to compare differences in the rates of operative complications, conversions to laparotomy, and postoperative admissions after laparoscopy. We also estimated the influence of medical history and specific laparoscopic procedures on the risk of adverse complications after surgery. RESULTS: Operative complications and conversion to laparotomy occurred in 1.9% and 4.7% of laparoscopic procedures, respectively. Complications included four bowel, two bladder, one ureteral, two vascular, and five abdominal wall injuries. There were 165 patients (19.6%) admitted postoperatively. Aside from the type of operative procedure, increasing age was the most important predictor of complications. Relative to all other operative procedures, women treated for endometriosis or ovarian cystectomy had generally low rates of operative complications, conversions to laparotomy, and postoperative admissions. In contrast, 12.5% of women undergoing laparoscopically assisted vaginal hysterectomy experienced operative injuries or abdominal bleeding and 90% were hospitalized postoperatively. CONCLUSION: Serious operative complications after gynecologic laparoscopy were rare in this patient population. The more complex laparoscopic procedures resulted in proportionately greater rates of operative complications, conversions to laparotomy, and postoperative admissions to the hospital.