Context:
Progesterone promotes uterine relaxation during pregnancy and its withdrawal induces labor. Progesterone withdrawal in human parturition is mediated in part by changes in the relative levels ...of the nuclear progesterone receptor isoforms, PR-A and PR-B, in myometrial cells. Parturition also involves myometrial inflammation; however, the functional link between nuclear PR-mediated progesterone actions and inflammation in human myometrial cells is unclear.
Objective:
Our objective was to determine how PR-A and PR-B regulate progesterone action in human myometrial cells and specifically the expression of genes encoding contraction-associated proteins and proinflammatory mediators.
Design:
Effects of PR-A and PR-B on the capacity for progesterone to modulate gene expression was determined using an immortalized human myometrial cell line stably transfected with inducible PR-A and PR-B expression transgenes and conditioned to express various PR-A and PR-B levels. Gene expression was assessed by genome wide transcriptome analysis, quantitative RT-PCR and immunoblotting.
Results:
PR-A and PR-B were each transcriptionally active in response to progesterone and affected the expression of distinct gene cohorts. The capacity for progesterone to affect gene expression was dependent on the PR-A to PR-B ratio. This was especially apparent for the expression of proinflammatory genes. Progesterone decreased proinflammatory gene expression when the PR-A to PR-B ratio favored PR-B and increased proinflammatory gene expression when the ratio favored PR-A. Progesterone via PR-B increased expression of inhibitor-κBα, a repressor of the nuclear factor-κB transcription factor, and inhibited basal and lipopolysaccharide-induced proinflammatory gene expression. Both of those PR-B-mediated effects were inhibited by PR-A.
Conclusions:
Our data suggest that during most of human pregnancy, when myometrial cells are PR-B dominant, progesterone promotes myometrial quiescence through PR-B-mediated antiinflammatory actions. At parturition, the rise in PR-A expression promotes labor by inhibiting the antiinflammatory actions of PR-B and stimulating proinflammatory gene expression in response to progesterone.
Current diagnosis and treatment of interstitial pregnancy Moawad, Nash S., MD; Mahajan, Sangeeta T., MD; Moniz, Michelle H., MD ...
American journal of obstetrics and gynecology,
2010, 2010-Jan, 2010-01-00, 20100101, Letnik:
202, Številka:
1
Journal Article
Recenzirano
The incidence of interstitial pregnancy is rising. Traditional treatment with laparotomy, hysterectomy, or cornual wedge resection is associated with high morbidity and detrimental effects on future ...fertility. A diverse array of alternate treatments has been introduced over the last 3 decades, with the common goal of achieving a minimally invasive, standardized management strategy. This has been facilitated by impressive strides towards prompt diagnosis, both radiologically and chemically. In this review, we explore the current state of the art diagnostic criteria and the clinically significant diverse therapeutic options with supporting literature. Finally, we propose a structured, best-practice management plan for the once-lethal interstitial pregnancy, based on the current literature.
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•Ovarian aging is one of the etiological factors in infertile women.•Mitochondrial dysfunction drives ovarian aging.•Rejuvenating mitochondria with nutrient therapy may improve ...fertility.•Optimizing mitochondria by lifestyle or environment prolongs reproductive longevity.•Mitochondrial replacement therapy for in vitro fertilization is being investigated.
Mitochondrial dysfunction is one of the hallmarks of aging. Consistently mitochondrial DNA (mtDNA) copy number and function decline with age in various tissues. There is increasing evidence to support that mitochondrial dysfunction drives ovarian aging. A decreased mtDNA copy number is also reported during ovarian aging. However, the mitochondrial mechanisms contributing to ovarian aging and infertility are not fully understood. Additionally, investigations into mitochondrial therapies to rejuvenate oocyte quality, select viable embryos and improve mitochondrial function may help enhance fertility or extend reproductive longevity in the future. These therapies include the use of mitochondrial replacement techniques, quantification of mtDNA copy number, and various pharmacologic and lifestyle measures. This review aims to describe the key evidence and current knowledge of the role of mitochondria in ovarian aging and identify the emerging potential options for therapy to extend reproductive longevity and improve fertility.
On the Road to Safer Morcellation Hurd, William W
Obstetrics and gynecology (New York. 1953),
2017-June, 2017-06-00, 20170601, Letnik:
129, Številka:
6
Journal Article
Minimally invasive hysterectomy has a number of well-documented advantages compared with open hysterectomy, including lower complication rates, lower cost, and faster recovery. In this retrospective ...study of almost 10,000 women undergoing minimally invasive hysterectomy for endometrial cancer, the investigators found that laparoscopic compared with open hysterectomy was associated with a decreased risk of venous thromboembolism (0.7% vs. 2.2%, respectively; P<.001). This relationship remained after correcting for age, body mass index, race, operative time, comorbidity index, and surgical complexity. It was assumed that the majority of these patients undergoing surgery for cancer received some form of venous thromboembolism prophylaxis.
To examine the effectiveness of hysteroscopy plus manual vacuum aspiration (MVA) for endometrial polypectomy compared with hysteroscopic morcellation.
Retrospective cohort study (Canadian Task Force ...classification II-2).
Duke University Medical Center database.
Women who underwent hysteroscopic removal of endometrial polyps performed by Duke Fertility Center faculty physicians between January 1, 2015, and January 29, 2018, using either hysteroscopy plus MVA or hysteroscopic morcellation.
The 2 groups were compared using the χ
or Fisher's exact test, Student's t test, and multivariable regression analysis.
The primary outcome was the duration of the procedure. Secondary outcomes were fluid deficit, rate of complete polyp resection, estimated blood loss, and operative complications. A total of 102 women undergoing endometrial polypectomy were identified. Patients in whom polyps were removed using only a hysteroscopic grasper and/or scissors (n = 31); patients who underwent an additional simultaneous procedure, such as laparoscopy (n = 12); and patients in whom the duration of the procedure was not recorded (n = 2) were excluded. Among the remaining 57 patients, 28 underwent hysteroscopy plus MVA and 29 underwent hysteroscopic morcellation. The mean duration of procedure was longer for hysteroscopic morcellation compared with hysteroscopy plus MVA (32 ± 10 minutes vs 20 ± 6 minutes; p = .04), and this difference remained significant after adjusting for age, body mass index, surgeon, and number and size of polyps. Mean fluid deficit was greater for morcellation than for hysteroscopy plus MVA (277 ± 204 mL vs 51 ± 97 mL; p < .001). Complete polyp resection was possible in all patients; however, the use of a hysteroscopic scissors and grasper was required for 1 patient in the MVA group. Estimated blood loss was minimal in all cases, and there were no operative complications.
Hysteroscopy plus MVA is an effective method for removing large or multiple endometrial polyps, with outcomes comparable to hysteroscopic morcellation.
Objective To determine whether gonadotropin-releasing hormone (GnRH) analog cotreatment with chemotherapy provides better reproductive outcomes for women at risk of premature ovarian failure (POF) as ...a side-effect of gonadotoxic chemotherapy. Design Systematic review and meta-analysis. Setting University-affiliated research centers. Patient(s) None. Intervention(s) Electronic and manual searches (e.g., MEDLINE, EMBASE, CENTRAL) up to January 2010 were performed to identify randomized controlled trials (RCTs) comparing GnRH cotreatment with chemotherapy alone in premenopausal women. Main Outcome Measure(s) Incidence of POF after treatment, incidence of women with resumption of ovulation, POF after an initial normal cycle, normal cycles but abnormal markers of ovarian reserve, spontaneous occurrence of pregnancy after treatment, and time to reestablishment of menstruation; data also extracted to allow for an intention-to-treat analysis. Result(s) Twenty-eight RCTs were identified, but only six met the inclusion criteria. Data were only available for the incidence of women with new onset of POF, resumption of ovulation, and occurrence of pregnancy. The incidence of POF or resumption of ovulation both demonstrated a statistically significant difference in favor of the GnRH cotreatment. The occurrence of spontaneous pregnancy showed no statistically significant difference between GnRH cotreatment and the control groups. Conclusion(s) Evidence from RCTs suggests a potential benefit of GnRH cotreatment with chemotherapy in premenopausal women, with higher rates of spontaneous resumption of menses and ovulation but not improvement in pregnancy rates. Data relating to study quality and possible bias for the majority of the outcomes in this review were not available, denoting possible selective reporting of trial data.
Conflicts of Interest and Medical Publishing Hurd, William W.
Obstetrics and gynecology (New York. 1953),
2013-September, 2013-Sep, 2013-09-00, 20130901, Letnik:
122, Številka:
3
Journal Article
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