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Biomedical subjects

W P Dmowski

Publications and source records attributed to W P Dmowski.

At least 19 recordsLinked to original sources
PubMed1995

The effect of endometriosis, its stage and activity, and of autoantibodies on in vitro fertilization and embryo transfer success rates.

OBJECTIVES: To analyze IVF cycle parameters, including pregnancy rates (PR), in women with and without endometriosis and to evaluate the effect of the stage and activity of endometriosis and of autoantibodies. DESIGN: A retrospective analysis of 237 consecutive IVF cycles (193 patients), 119 in women with and 118 without endometriosis. The endometriosis group was further subdivided according to the stage and activity of the disease and autoantibody positivity. SETTING: Hospital-based and freestanding IVF programs with the same IVF team. PATIENTS: One hundred ninety-three women of reproductive age undergoing IVF; 84 had prior diagnosis of endometriosis, and 109 had other indications for IVF. Within the endometriosis group, 40 did and 44 did not have evidence of active disease. Autoantibodies were measured in 50 patients. INTERVENTIONS: The IVF protocol was standard with GnRH agonist administered from the midluteal phase of the preceding cycle. Variables included the method of ET and the use of corticosteroids. MAIN OUTCOME MEASURES: Number of follicles produced, number of eggs retrieved, fertilization rates, number of embryos transferred, and PR per transfer. RESULTS: There was no difference between groups in the response to stimulation, number of oocytes retrieved, number fertilized, and number cleaved. The overall PR was 27% per transfer; it was similar in women with and without endometriosis (29% and 25%, respectively). There was also no difference in PR according to the stage or activity of the disease. However, PR in autoantibody-positive and -negative patients were significantly different (22.9% and 45.7%, respectively). Among autoantibody-positive patients treated with corticosteroids, 8 of 10 conceived. CONCLUSIONS: This study confirms previous reports that IVF success rates are comparable in women with and without endometriosis regardless of the activity and stage of the disease. However, our study also indicates that autoantibodies may affect adversely implantation of embryos and that this effect can be overcome by administration of corticosteroids.

Adult↗
PubMed1994

Effect of danazol in vitro and in vivo on monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis.

OBJECTIVE: To investigate danazol's effect in vitro and in vivo on the ability of peripheral blood monocytes (PBM) from women with endometriosis to stimulate endometrial cell proliferation. DESIGN: Uterine endometrial cells from untreated or danazol-treated patients with endometriosis were cultured with or without autologous or heterologous PBM in the presence of different concentrations of danazol for 72 hours before assessment of endometrial cell proliferation by thymidine incorporation. SETTING: Not for profit clinical research institute and academic cell culture laboratory. PATIENTS: Women of reproductive age undergoing laparoscopy for endometriosis, 19 untreated patients and 17 danazol-treated patients. INTERVENTIONS: Peripheral blood monocytes and endometrial biopsies obtained at laparoscopy. Danazol (800 mg/d) administered for 2 to 6 months (treated group) or added to cell cultures in concentrations of 10(-6), 10(-7), or 10(-9) M. RESULTS: Endometrial cell proliferation was enhanced by autologous or heterologous PBM from untreated patients with endometriosis but was unaffected or suppressed by PBM from danazol-treated patients. Danazol in vitro reduced PBM-enhanced endometrial cell proliferation. Endometrial cell proliferation from danazol-treated patients was not enhanced by PBM from untreated patients with endometriosis. CONCLUSIONS: Danazol treatment in vitro or in vivo suppresses PBM-mediated enhancement of endometrial cell proliferation. The effects are against both PBM and endometrial cells, suggesting that danazol affects monocyte-derived growth-stimulating factors and endometrial cell response to growth-stimulating factors.

Adult↗
PubMed1994

The role of cell-mediated immunity in pathogenesis of endometriosis.

It is well recognized that cell-mediated immune responses contribute to the elimination of foreign antigens and cells from the invading organism. It is also likely that the immune system can recognize and eliminate altered or misplaced autologous cells such as ectopic endometrial cells. This mechanism may be operative in most women, preventing the development of endometriosis. Recent studies in women with endometriosis demonstrate functional changes in cells of the immune system including monocytes/macrophages, natural killer cells, cytotoxic T-lymphocytes and B cells. These changes suggest decreased surveillance, recognition and destruction of the misplaced endometrial cells and possible facilitation of their implantation and development of endometriosis. Peripheral blood monocytes (PBM) and peritoneal macrophages (PM) may play a key role in this respect, and may control the function of other immune cells. We have demonstrated that in normal fertile women without endometriosis, PBM and PM suppress endometrial cell proliferation in vitro. In endometriosis, PBM stimulate and PM inhibit endometrial cell proliferation and the cytotoxic effect of PM is inversely correlated with the stage of the disease. The decrease in PM cytotoxic function is controlled by prostaglandin synthesis. In infertile women without endometriosis, the effects of PM and PBM are variable. In about one third of patients, the effects of PM and PBM suggest subclinical endometriosis; in the remaining two thirds of patients the effects of PM and PBM are similar to those of fertile controls. Interestingly, endometrial cells in women with endometriosis are more sensitive to the stimulatory effect of PBM, and more resistant to the cytotoxicity of the immune cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1992

Laparoscopic myomectomy.

Fifty-six patients presenting with infertility (17); bleeding, pain, and pressure symptoms (32); and pelvic mass (seven) associated with leiomyomas were managed with laparoscopic myomectomy. Twenty-four second-look procedures were performed to evaluate healing and adhesion formation. Operative time ranged between 45-443 minutes (mean 157), estimated blood loss varied from 10-400 mL (mean 75), and the mean length of hospital stay was 1 day. Traditional morcellation was used initially but was abandoned because of long operating time; vaginal or abdominal removal (depending on size) proved more satisfactory. Three patients developed subcutaneous emphysema and one had febrile morbidity due to upper respiratory tract infection. There were no other complications. In 24 second-look procedures, adhesions were present in 16 subjects (66%). Twelve of 17 in the infertility group conceived (71%); all 39 patients with other complaints experienced satisfactory relief. There were no reoperations. When myomectomy is indicated, the laparoscopic approach appears to offer an alternative to abdominal surgery in selected patients.

Adult↗
PubMed1992

The development of cytotoxicity in peritoneal macrophages from women with endometriosis.

OBJECTIVE: To assess the activation status of peritoneal macrophages from women with endometriosis. DESIGN: Peritoneal macrophages from patients undergoing laparoscopy were tested for cytotoxic activity against a cultured hepatoma cell line. SETTING: Patients were tested at initial laparoscopy or at the completion of therapy. PATIENTS AND PARTICIPANTS: Fertile controls (n = 27), infertile controls (n = 20), untreated endometriosis (n = 43), danazol-treated endometriosis (n = 22), and gonadotropin-releasing hormone agonist (GnRH-a)-treated endometriosis (n = 13) were tested. INTERVENTIONS: Danazol (800 mg/d) or GnRH-a therapy for 6 months. RESULTS: Cytotoxicity was elevated in stage I and II endometriosis (P less than 0.02) and in infertile controls (P less than 0.05) compared with fertile controls. Cytotoxicity in stage III and IV endometriosis was lower (P less than 0.02) than in stage I and II endometriosis. Indomethacin in vitro increased cytotoxicity (P less than 0.05) in stage III and IV endometriosis but not in the other groups tested. Cytotoxicity in danazol or GnRH-a-treated patients was increased (P less than 0.05 or greater) compared with untreated patients with comparable stage of disease. CONCLUSIONS: Peritoneal macrophage cytotoxicity in women with endometriosis is affected by (1) the extent of endometriosis, (2) prostaglandin metabolism, and (3) treatment with danazol or GnRH-a.

Cytotoxicity, Immunologic↗
PubMed1990

Progesterone:estradiol ratios at implantation in ongoing pregnancies, abortions, and nonconception cycles resulting from ovulation induction.

UNLABELLED: The purpose of this study was to compare progesterone (P):estradiol (E2) ratios after ovulation induction at the time of implantation in cycles resulting in ongoing pregnancies or abortions and in nonconception cycles. Material included 43 stimulated conception cycles, 29 with human menopausal gonadotropins (hMG) and human chorionic gonadotropins (hCG), 14 with clomiphene citrate (CC) with or without hCG, and 28 nonconception cycles (13 hMG and hCG, 15 CC with or without hCG). Midluteal P and E2 were measured and expressed in ng/mL. There were no differences in P:E2 ratios (mean +/- SE) for ongoing pregnancies after hMG and hCG (n = 20, 112.6 +/- 14.9), CC and hCG (n = 6, 97.0 +/- 15.9), or CC alone (n = 5, 96.2 +/- 25.5), and the data were pooled. Progesterone:estradiol ratios in 31 ongoing pregnancies and 28 nonconception cycles were 107.0 +/- 10.7 and 115.2 +/- 12.5, respectively, both significantly higher than in 12 abortions (64.5 +/- 13.2). IN CONCLUSION: (1) P:E2 ratios at the time of implantation were similar after CC with or without hCG and hMG and hCG treatment; (2) high luteal P:E2 ratio was associated with ongoing pregnancies; and (3) lower P:E2 ratio was seen in cycles leading to spontaneous abortion.

Abortion, Spontaneous↗
PubMed1990

Danazol. A synthetic steroid with diverse biologic effects.

Danocrine (danazol) is a synthetic steroid with multiple and diverse biologic effects. It exerts these effects by binding to steroid transport proteins in the circulation and to specific receptors in target tissues. Centrally, danazol inhibits gonadotropins, suppressing gametogenesis and steroidogenesis. Gonadal and adrenal steroidogenesis are suppressed further through danazol's direct effect on specific enzyme systems. Danazol also displays immunoregulatory effects both in vivo and in vitro. In endometriosis, danazol induces amenorrhea and a hypoestrogenic state, resulting in endometrial atrophy. The drug's direct binding to androgen and progesterone receptors in endometriotic tissue may contribute further to the suppression of endometriosis. In women with endometriosis who produce autoantibodies against endometrial cells and endometrial cell-derived phospholipids, histones and nucleotides, danazol may improve reproductive performance through the suppression of abnormal autoantibody levels. In several other autoimmune and genetic disorders danazol brings about a clinical improvement by lowering abnormal autoantibody production or by increasing the concentration of genetically deficient protein. In order to explore the full clinical potential of the drug and to better understand danazol's mechanism of action and especially its immunoregulatory effects in autoimmune diseases and endometriosis, further investigation is necessary.

Animals↗
PubMed1989

A randomized, prospective comparison of endocrine changes induced with intranasal leuprolide or danazol for treatment of endometriosis.

A prospective, randomized trial compared hormonal changes induced with intranasal leuprolide 1.6 mg/day to danazol 800 mg/day for treatment of endometriosis. Both regimens induced anovulation and ovarian suppression in all subjects. Mean estradiol (E2) and progesterone (P) levels were suppressed with both regimens, but were lower with leuprolide. There was no difference in cumulative follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, although at times during treatment mean levels of these hormones were lower with leuprolide. Higher P levels in the danazol group, most likely of adrenal origin, indicated a suppressive effect on adrenal steroidogenesis. Symptomatic improvement was significant in both groups. Laparoscopy after treatment also demonstrated a decrease in endometriosis scores in both groups. At 12 months after treatment, cumulative pregnancy and live birth rates were similar in both groups. Leuprolide offers an attractive alternative to danazol for the medical treatment of endometriosis.

Administration, Intranasal↗
PubMed1989

Ovarian suppression induced with Buserelin or danazol in the management of endometriosis: a randomized, comparative study.

The effectiveness of Buserelin (Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ) (0.2 mg subcutaneously [SC] or 1.2 mg intranasally [IN] per day) and danazol (800 mg per day) in inducing ovarian suppression for the management of endometriosis was compared in a prospective randomized study. During 6 months of treatment, peripheral follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol concentrations were suppressed to a similar degree in both groups. Symptomatic improvement and laparoscopically assessed regression of endometriotic lesions also were comparable. After treatment, 8 of 18 infertile women treated with Buserelin and 5 of 8 treated with danazol conceived. General and hypoestrogenic side effects were similar in both groups, while androgenic and anabolic were more frequent with danazol. High density lipoprotein (HDL)-cholesterol increased in the Buserelin and decreased in the danazol group. The study indicates that at the dose tested, buserelin and danazol induce a similar degree of ovarian suppression resulting in a comparable clinical improvement and regression of endometriotic lesions.

Adult↗
PubMed1989

Immunologic aspects of endometriosis.

Endometriosis appears to be a systemic disease with alterations in both humoral and cell-mediated immunity. An immune defect may allow ectopic implantation of the endometrial cells with subsequent development of autoantibodies.

Endometriosis↗
PubMed1988

Rhesus monkey sperm penetration into zona-free hamster ova: comparison of preparation and culture conditions.

A major problem in development of nonhuman primate in vitro fertilization is the selection of donor males and repeated collection of consistent sperm samples. In practice, collection of a viable semen sample is highly dependent on operator technique and the type of animal restraint. We report an updated method for semen collection from the rhesus monkey (Macaca mulatta), use of TES-Tris (TEST) Yolk Buffer (TYB) for prolonged sperm storage and improved results of hamster ovum penetration assay. Semen was obtained from adult males restrained with 2.0 mg/kg IM ketamine hydrochloride prior to direct penile stimulation (Grass SD-9, frequency 150, delay 9, duration 7, volts 12-18, repeat mode, twin pulse). Liquified semen was washed and centrifuged twice at 100 X g for 5 min in BWW, Ham's F-10 and TALP and allowed to swim-up 60 min at 37 degrees in 5% CO2 and air. Alternatively, semen was mixed 1:1 with TYB, refrigerated 20 h at 4 degrees C, centrifuged at 100 X g for 5 min, and the pellet resuspended in 1.0 ml of TALP or BWW prior to use. Hamster ova penetration was achieved with capacitated macaque sperm. Penetration was significantly improved (P less than .001) with preincubation in TYB followed by resuspension in TALP (79%).

Animals↗
PubMed1988

Cryopreservation of in vitro-fertilized human embryos: histologic and cytogenetic analysis of an ectopic conceptus.

In this study, 39 embryos from 17 patients were cryopreserved in a Planer R204 cell freezer using the protocol of Mohr et al. (J Vitro Fert Embryo Transfer 2:1-10, 1985). The procedure was modified by supplementing the cryoprotectant with 10% heat-inactivated and filtered (0.22 micron) maternal serum instead of fetal calf serum, and embryos were frozen in 500-microliter plastic straws instead of glass ampoules. After 12-25 weeks of storage in liquid nitrogen, 12 embryos from six patients were thawed at 8.0 degrees C min to room temperature, incubated in 75% maternal serum with Ham's F-10, and replaced in utero. One pregnancy occurred. The patient was a 34-year-old nulligravida with occluded fallopian tubes. A year prior, she conceived triplets from three embryos during an in vitro fertilization (IVF) cycle, but she delivered at 21 weeks and the infants did not survive. The second IVF attempt produced four embryos. Two were replaced during the IVF cycle, but they did not implant. Two were cryopreserved and replaced 25 weeks later. On day 28 after replacement, beta human chorionic gonadotropin (beta-hCG) was 4126 IU, but there was no gestational sac in utero on ultrasonographic examination. Laparoscopy disclosed a right tubal pregnancy which was removed with the fallopian tube. Histological examination demonstrated normal chorionic villi. The chromosomal pattern was 46 XX by direct analysis and cell culture.

Adult↗
PubMed1988

Recurrent endometriosis following hysterectomy and oophorectomy: the role of residual ovarian fragments.

Seven women with recurrent endometriosis after definitive surgery were evaluated. Plasma estradiol, FSH and LH indicated that recurrence was stimulated by residual ovarian fragments in six and pseudopregnancy regimen in one. Surgical treatment in two women was followed in one by hypertrophy of another ovarian fragment and reactivation of endometriosis as demonstrated by serial endocrine and ultrasonographic studies. Three patients responded well to hormonal treatment; one required pelvic irradiation. We conclude that: (1) small ovarian fragments may hypertrophy under increased gonadrotropin stimulation, become functional and stimulate recurrence of endometriosis; (2) resection of one such fragment may be followed by reactivation of another.

Adult↗
PubMed1988

Persistent ovarian cysts following administration of human menopausal and chorionic gonadotropins: an attenuated form of ovarian hyperstimulation syndrome.

Ovarian cysts persisting after the onset of menses were demonstrated by ultrasound (US) in 40 of 71 (56%) nonconception cycles following ovulation induction with human menopausal gonadotropins (hMG) and human chorionic gonadotropin (hCG). Persistent cysts were self-limited and all resolved spontaneously within two cycles. They developed more frequently during stimulation cycles with (1) higher mean pre-hCG serum estradiol (E2), (2) a greater number of medium and large follicles at peak pre-hCG E2, and (3) a larger leading follicle diameter at peak pre-hCG E2. Persistent ovarian cysts frequently occurred despite a peak pre-hCG E2 lower than 1000 pg/ml. Although ovarian enlargement in the presence of cysts exceeded 5 X 5 cm in 25% of cases, no patient developed clinical symptoms of ovarian hyperstimulation syndrome (OHSS). Repeated induction of ovulation with hMG/hCG in the presence of nonfunctional, persistent cysts resulted in pregnancies in 6 of 15 cases (40%). Asymptomatic persistent ovarian cysts frequently follow an hMG/hCG regimen and, when nonfunctional, are not a contraindication to repeated ovarian stimulation. Persistent ovarian cysts appear to be an attenuated form of OHSS.

Adult↗
PubMed1988

Effects of danazol, gonadotropin-releasing hormone agonist, and estrogen/progestogen combination on experimental endometriosis in the ovariectomized rat.

Direct effects of a gonadotropin-releasing hormone agonist (GnRHa), danazol, or estrogen/progestogen (E/P) on experimental endometriosis were evaluated in castrated female rats. Endometrial explants decreased in size following castration, but there was no further change in the treatment groups. Histologic examination indicated atrophy and regression of experimental endometriosis in all groups of castrated animals. As expected, following castration, serum estradiol (E2) became undetectable, serum progesterone (P4) decreased, and cytosolic E2 and P4 binding capacity in the endometrial explants was lower. However, in danazol-treated animals, serum P4 and E2 receptor concentrations were significantly higher than in all other castrated groups, and in both danazol and E/P treated animals, concentrations of P4 receptor were significantly higher than in castrated controls. In contrast, GnRHa treatment had no effect on serum E2 and P4 levels nor on E2 or P4 receptors. The authors conclude that danazol and E/P preparations may have a direct effect on the ectopic endometrium through interaction with steroid receptors.

Animals↗