Iatrogenic bladder injury following gynecologic and obstetric surgery: A systematic review and meta-analysis.

INTRODUCTION: Iatrogenic bladder injury is a rare complication following obstetric and gynecologic surgery and only sparse information is available regarding length of transurethral catheterization following injuries, suturing techniques including choice of suture, and complications. The primary aim of this systematic review was to evaluate length of transurethral catheterization in relation to complications following iatrogenic bladder injury. Second, we aimed to evaluate the number of complications following repair of iatrogenic bladder injuries and to describe suture technique and best choice of suture. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted, and the results were presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and Medline electronic databases were searched, and followed by screening from two independent reviewers. Studies published between January 2000 and March 2023 describing methods of bladder injury repair following obstetric or gynecologic benign surgery were included. Data extraction was done using Covidence. We performed a meta-analysis on complications after repair and explored this with a meta-regression analysis (Metafor package R) on length of catheterization to determine if length of catheterization influenced the risk of complication. A risk of bias tool from Cochrane was used to assess risk of bias and the study was registered in PROSPERO (CRD42021290586). RESULTS: Out of 2175 articles, we included 21 retrospective studies, four prospective studies, and one case-control study. In total, 595 bladder injuries were included. Cesarean section was the most prominent surgery type, followed by laparoscopically assisted vaginal hysterectomy. We found no statistically significant association between length of transurethral catheterization and numbers of complications following repair of iatrogenic bladder injuries. More than 90% of injuries were recognized intraoperatively. Approximately 1% had complications following iatrogenic bladder injury repair (0.010, 95% confidence interval 0.0015-0.0189, 26 studies, 595 participants, I2 = 4%). CONCLUSIONS: Our review did not identify conclusive evidence on the length of postoperative catheterization following bladder injury warranting further research. However, the rate of complications was low following iatrogenic bladder injury with a wide range of repair approaches.

Iatrogenic bladder and ureteral injuries following gynecological and obstetric surgery.

KEY MESSAGE: Ureteral injuries are often associated with complications and risk of fistula especially in case of malignancy. Length of catheterization should be reconsidered according to the injury. PURPOSE: Iatrogenic urinary tract injuries are potential complications of gynecologic and obstetric surgery. Our aim was to describe suture type and size, length of urethral catheterization, length of hospitalization, reoperation rate, follow-up, and impact on quality of life following iatrogenic bladder and ureteral injury. METHODS: In total, 81 women met inclusion criteria. Bladder injuries included 55 women, ureteral injuries in 23 women, and three women had bladder and ureteral injuries. RESULTS: Most bladder injuries were managed by a two-layer suture followed by transurethral catheterization for 11.4 days (95% CI 9.1-13.6). The most frequent suture type was 3.0 Vicryl in all subgroups. In total, 30.4% of ureteral injuries were managed by neoimplantation followed by ureteral stenting for 38.0 days (95% CI 22.0-54.0) and transurethral catheterization for 16.9 days (95% CI 5.3-28.4), or by ureteral stenting for 46.7 days (95% CI 31.5-61.2) and transurethral catheterization for 6.25 days (95% CI 1.0-13.5). Altogether, 25 (30.9%) women underwent a reoperation mostly due to ureteral injury (68%). In total six women developed a fistula, of whom five had malignant surgery. Multiple linear regression showed a statistically significant increased median length of urethral catheterization when the duration of surgery increased. CONCLUSIONS: Our study demonstrates a high reoperation rate, and a high fistula rate in case of malignancy. Length of catheterization was high even in case of benign surgery, however, only one woman developed a fistula in the benign group, suggesting a reduction in catheterization length.

Lateral coagulation of the uterine artery at its origin prior to total laparoscopic hysterectomy. A randomized control trial.

BACKGROUND AND OBJECTIVES: Lateral occlusion prior to TLH has been suggested to reduce perioperative bleeding, operative time, and hospital stay. Furthermore, reducing the amount of bleeding and the length of the operation may affect parameters such as postoperative pain and the number of patients with postoperative vaginal vault hematoma. METHODS: This RCT was conducted at a single center at Odense University Hospital in Denmark. Between February 2016 and February 2019, a total of 58 patients undergoing TLH and bilateral salpingectomy for benign cases were recruited to the study. RESULTS: The mean operating time was significantly longer in the LA group with a mean difference between the two groups of six minutes. No other discrepancy regarding the primary outcomes was observed between the two groups. Total blood loss was similar in the two groups as well as the average hospital stay and the VAS score during the first seven days. 93% of the patients were discharged from the hospital within the first 24 h postoperatively. CONCLUSION: This RCT demonstrates that lateral occlusion of the uterine artery prior to TLH does not improve outcome for the patients and should therefore not be used as a standard procedure.

Lateral closure of the uterine artery prior to laparoscopic hysterectomy: a systematic review.

An alternative surgical technique with closure of the uterine artery at its origin, known as lateral approach prior to TLH, has been proposed and it may offer important benefits to both patients and surgeons. Our objectives were to review the current literature regarding surgical outcomes between lateral and conventional approach in relation to TLH. We followed the 'PRISMA' guidelines and conducted a systematic review, which involved searching PubMed and Embase databases for RCTs evaluating the topic. We identified four RCTs including 585 patients. Three of the four studies reported a significant lower bleeding during TLH with prior lateral approach. Operative time was also shorter in the lateral approach group compared to the conventional approach group in three studies.Our review provides evidence that lateral occlusion of the uterine arteries prior to total laparoscopic hysterectomy may be beneficial due to less blood loss and shorter perioperative time without compromising patient safety.

Efficacy and safety of pelvic organ prolapse surgery with porcine small intestinal submucosa graft implantation.

OBJECTIVE: The ideal implant material for the surgical repair of pelvic organ prolapse in women is yet to be found. This retrospective study aims to evaluate a porcine small intestinal submucosa (SIS) graft (Surgisis™). STUDY DESIGN: We reviewed the medical records of women that were operated upon for pelvic organ prolapse using implantation of SIS graft and we examined the short-term complications and recurrence rates. RESULTS: A total of 155 surgical procedures were reviewed. SIS graft was placed in the anterior, posterior and middle compartments in 93 (60%), 71 (45.8%) and 13 (8.4%) cases, respectively. At three-month follow-up, 22.6% of anterior graft repairs displayed anatomical recurrence (POP-Q stage ≥ 2), compared to 4.8% of posterior and none of the middle compartment graft repairs. During the three postoperative months, 56% of the women were recorded with complications, mostly urinary retention (19%) and pain (12%). The incidence of grade III complications was 5.3%. Persistent complications at three months were observed in 28% of all cases. Logistic regression analysis showed that previous prolapse surgery at the same compartment was a significant predictor for recurrence of prolapse after SIS graft application, whereas lower age, smoking and longer duration of surgery were significant predictors for the development of complications. Younger women had higher risk of developing pain postoperatively. CONCLUSION: Pain and urinary tract symptoms hold a central position in the complications profile of SIS graft-augmented prolapse surgery. The relatively high recurrence rates do not suggest a clear benefit from SIS graft use.

Is abdominal hysterectomy still the surgery of choice in sub-Saharan Africa?

A trend toward minimally invasive surgery is increasing worldwide. However, reports on the extent and the role of vaginal or laparoscopic hysterectomy in benign gynecologic surgery in sub-Saharan Africa are scarce. Our commentary aims to highlight the existing gaps and potential barriers to implementation of vaginal or laparoscopic hysterectomy and suggests how to introduce and expand minimally invasive gynecologic surgery in this region. Little documentation exists in the literature to account for the role of minimally invasive surgery in the sub-Saharan Africa. Hysterectomy for benign reasons is commonly performed by the abdominal approach. This approach is accompanied by significant complications, prolonged hospitalization, and longer recovery duration. Our commentary highlights the importance of investigating region-specific barriers to the practice of minimally invasive gynecologic surgery in sub-Saharan Africa.

Combined transcervical endometrial resection and levonorgestrel device treatment compared to transcervical endometrial resection for abnormal uterine bleed.

INTRODUCTION: Transcervical resection of the endometrium (TCRE) is a first-line surgical treatment of abnormal uterine bleeding. However, many women experience unsuccessful results, causing hysterectomy in up 17% of cases. The aim of this study was to describe the odds of hysterectomy in women with abnormal uterine bleeding, treated with TCRE and levonorgestrel intrauterine contraceptive device (TCRE + LNG-IUCD) or TCRE alone. The secondary aim was to analyze the rate of amenorrhea. MATERIAL AND METHODS: Designed as a retrospective cohort study, and conducted at Odense University Hospital, Denmark, the study included women with abnormal uterine bleeding, who underwent TCRE from January 2013 to December 2015. The decision of treatment with respect to LNG-IUCD was at the woman's discretion. Data were collected from medical records and a self-reported retrospective bleeding-pattern questionnaire. A multivariate regression model was used, enabling adjustment for potential and identified confounders. RESULTS: Out of 432 women, 276 (62%) consented to inclusion and of these, 16 (4%) were excluded. In total 88 (34%) received combined treatment and 172 (66%) received TCRE alone. Ten women (11%) treated with TCRE + LNG-IUCD underwent hysterectomy, compared with 27 (16%) treated with TCRE alone (OR = 0.69, 95% CI 0.28-1.56; P = .34). Multivariate analysis disclosed a significant effect of TCRE + LNG-IUCD (OR = 0.35, 95% CI 0.13-0.97; P = .04) on hysterectomy. The presence of fibromas was shown to increase the odds of treatment failure, resulting in hysterectomy (OR 2.69, 95% CI 1.15-6.31; P = .02). Furthermore, the incidence of amenorrhea was 59% in the TCRE + LNG-IUCD group and 36% in the TCRE alone group (OR = 2.56, 95% CI 1.46-4.49; P < .01). CONCLUSIONS: The study showed significantly lower odds of hysterectomy in the TCRE + LNG-IUCD group when adjusted for confounders. Combination treatment improves the bleeding patterns significantly compared with monotherapy with TCRE.

Robot assisted surgery during the COVID-19 pandemic, especially for gynecological cancer: a statement of the Society of European Robotic Gynaecological Surgery (SERGS).

All surgery performed in an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, irrespective of the known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) status of the patient, should be regarded as high risk and protection of the surgical team at the bedside should be at the highest level. Robot assisted surgery (RAS) may help to reduce hospital stay for patients that urgently need complex-oncological-surgery, thus making room for COVID-19 patients. In comparison to open or conventional laparoscopic surgery, RAS potentially reduces not only contamination with body fluids and surgical gasses of the surgical area but also the number of directly exposed medical staff. A prerequisite is that general surgical precautions under COVID-19 circumstances must be taken, with the addition of prevention of gas leakage: • Use highest protection level III for bedside assistant, but level II for console surgeon. • Reduce the number of staff at the operation room. • Ensure safe and effective gas evacuation. • Reduce the intra-abdominal pressure to 8 mmHg or below. • Minimize electrocautery power and avoid use of ultrasonic sealing devices. • Surgeons should avoid contact outside theater (both in and out of the hospital).

Two-dimensional (2D) versus three-dimensional (3D) laparoscopy for vaginal cuff closure by surgeons-in-training: a randomized controlled trial.

BACKGROUND: Objective evidence is lacking as to the benefit of the addition of 3D vision to conventional laparoscopy in Gynecologic surgery. This study aims to compare 3-D visual system to traditional 2-D laparoscopic visualization for the laparoscopic closure of the vaginal cuff during total laparoscopic hysterectomy by surgeons-in-training [defined as senior OBGYN resident or Minimally Invasive Gynecologic Surgery (MIGS) fellow]. METHODS: 51 patients undergoing total laparoscopic hysterectomy at two tertiary care academic hospitals were randomized to two-dimensional or three-dimensional vision system with cuff closure performed by surgeons-in-training. The primary outcome was the time taken for vaginal cuff closure. Secondary outcomes included peri-operative outcomes and assessment of surgeon's perception of ease of cuff closure. RESULTS: 27 (52.9%) cases were allocated to cuff closure with the 2D system and 24 (47.1%) cases to closure with the 3D vision system. Patient baseline characteristics were similar between the vision systems. Mean vaginal cuff closure time was not significantly different between 2D and 3D vision (10.1 min for 2D versus 12 min for 3D, p = 0.31). An additional 24 s was added to cuff closure time with each 1 kg/m2 increase in BMI, after controlling for potential confounders (p = 0.003). There was no difference in the surgeon rating of ease of cuff closure between 2D and 3D. Peri-operative outcomes are similar among the two groups. CONCLUSION: We did not demonstrate any benefits of 3D vision system over conventional 2D for the task of laparoscopic vaginal cuff suturing performed by surgeons-in-training. RCT Registration Number NCT02192606 https://clinicaltrials.gov/ct2/show/NCT02192606 (July 17, 2014).

Impact of per-operative antibiotics on the urinary tract infection rate following mid-urethral sling surgery for urinary incontinence: a randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The objective was to compare the effect of antibiotics versus no antibiotics prophylaxis per-operatively on the frequency of urinary tract infection (UTI) following mid-urethral sling application to treat stress or mixed urinary incontinence. METHODS: This study was designed as a multicenter prospective randomized trial. Women were included from eight centers in three countries. Women were aged under 60 years and had objectively verified stress urinary incontinence. Women with mixed urinary incontinence were also included. Randomization was held in blocks for operation with either antibiotics or no antibiotics. UTI was defined in accordance with the Centers for Disease Control (CDC) criteria for symptomatic UTI. Women were followed up at 3, 12, and 36 months. This was part of a trial comparing subjective cure rate in relation to application of Ajust® (single-incision mid-urethral slings) versus standard mid-urethral slings. RESULTS: The main outcome was to evaluate if per-operative antibiotics had any impact on UTI following sling surgery. In total, 305 women were randomized (158 [52%] to antibiotics and 147 [48%] to no antibiotics). Demographic data disclosed no differences between the two groups. The trial did not show any difference between the two groups regarding the frequency of postoperative UTI. Logistic regression analysis disclosed only residual urine volume at 3 months' follow-up as a significant risk factor for UTIs. Per-operative antibiotics had no influence on the frequency of mesh erosions or any other complication. CONCLUSIONS: Our trial does not suggest any beneficial effect of per-operative antibiotics on the risk of post-operative UTIs.

Feeling lucky: hierarchies of suffering and stories of endometrial cancer in a Danish context.

Illness stories are a prime analytical way of understanding patient perspectives on cancer. Nevertheless, limited studies have focused on stories of endometrial cancer. An ethnographic study including participant observation and interviews among 18 Danish women with endometrial cancer was conducted to examine prevalent stories and the ways the women responded to them. In this article, the analysis focuses on two exemplary cases, which present a line of issues related to the kinds of experiences that suffering includes. Findings illustrate that feelings of luck were central to the experience of being diagnosed, treated and cured, which was related to the way health professionals framed endometrial cancer as favourable through notions of curable/incurable, trivial and gentle/invasive and brutal, and aggressive/non-aggressive. Drawing upon the concept of a 'hierarchy of suffering', we exemplify how women tended to scale own experiences of suffering against others', leading some to believe they were not in a legitimate position to draw attention to themselves nor seek help and support, despite adverse physical, psychosocial effects. Thus, feelings of being lucky were intertwined with a sense of ambivalence. We conclude by discussing how suffering arises within a moral context, suggesting that the ways we speak of cancer may make some experiences unspeakable. This calls for increased clinical attention to more diverse narratives of cancer.

"But this is a good cancer:" Patient perceptions of endometrial cancer in Denmark.

AIMS AND OBJECTIVES: To explore endometrial cancer patients' perceptions of the disease and the influence of favourable prognoses on their experiences. BACKGROUND: Endometrial cancer is associated with favourable prognoses, which may imply that patients experience distress to a lesser extent than other cancer patients with less positive treatment outcomes. However, most people with cancer report reduced quality of life and, despite endometrial cancer being prevalent worldwide, experiences of the disease have been little explored. DESIGN: Ethnographic fieldwork with participant observations and interviews. METHODS: Observations during clinical consultations at two Danish hospitals and interviews with women with endometrial cancer (n = 18) over a period of 6 months. The article adheres to the COREQ guidelines for reporting qualitative research. RESULTS: We identify how patients consider cancer in general very likely to be fatal, while clinicians in contrast characterise endometrial cancer specifically as "good" because of favourable prognoses. We employ the concept of bricolage to illustrate how bits and pieces of biomedical knowledge and statistical evidence become intertwined with patients' past experiences and subjective ways of knowing, suggesting that patients' perceptions of endometrial cancer as a disease are somewhat dynamic. CONCLUSIONS: Public stories and everyday life experiences of cancer provide a central framework for illness perceptions. As a result, patients retain the idea of a close connection between cancer and death, while also adopting the notion of endometrial cancer as "good". This influenced how women responded to treatment and care. Framing endometrial cancer as "good" is not always helpful, as the impact of a cancer diagnosis per se is rarely favourable. RELEVANCE TO CLINICAL PRACTICE: In providing women with endometrial cancer with optimal support through diagnosis and treatment, clinicians should attend to the complexity of patients' illness understandings and be aware that assuring patients of a good prognosis not always has the expected impact.

Questionnaire-based evaluation of sexual life after laparoscopic surgery for endometriosis: a systematic review of prospective studies.

INTRODUCTION: Endometriosis is a benign disease that affects women of reproductive age. Laparoscopic excision of endometriotic implants is considered one of the most effective therapeutic options. The disease and its treatment can have a major impact on psychosexual well-being but this is often overlooked as most studies focus on pain instead of sexuality in a holistic approach. The aim of this study was to review the current literature regarding the effect of laparoscopic surgery for endometriosis on quality of sexual life (QoSL). MATERIAL AND METHODS: Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines we conducted a systematic review that involved searching PubMed and Embase databases for prospective studies evaluating the effect of laparoscopic surgery for endometriosis on QoSL, using validated questionnaires. RESULTS: Of 357 papers, 17 were selected for full text evaluation. Twelve studies using seven different questionnaires fulfilled the inclusion criteria. All studies reported improvements in QoSL following laparoscopic surgery for endometriosis. A meta-analysis could not be performed due to substantial heterogeneity among the included studies arising from differences in questionnaires, follow-up duration, stages of endometriosis, use of hormonal treatment, and missing data. CONCLUSIONS: Laparoscopic excision of endometriosis can improve QoSL. However, there is a need for randomized controlled trials based on a new validated questionnaire regarding specifically QoSL in association with endometriosis. As sexual functioning is a complex phenomenon driven by multiple physical, psychological and social factors, QoSL should be holistically evaluated by a team of different healthcare providers, implementing treatment programs that are individualized to each woman.

[Uterine fibroids].

Uterine fibroids are common, and only women with symptoms need treatment. Hysterectomy has been the most common treatment, but current management strategies offer a wide variety of treatment options ranging from medical, radiological to surgical treatment. The treatment needs to be individualized to each patient according to symptoms, age, number and position of fibroids and wish for future fertility.

Systematic review of the limited evidence for different surgical techniques at benign hysterectomy: A clinical guideline initiated by the Danish Health Authority.

Hysterectomy for benign gynecological conditions is a common operation that has developed extensively through the last 20 years. Methods and surgical techniques vary throughout the regions in Denmark as well as internationally. Consequently, the Danish Health Authority initiated a national clinical guideline on the subject based on a systematic review of the literature. A guideline panel of seven gynecologists formulated the clinical questions for the guideline. A search specialist performed the comprehensive literature search. The guideline panel reviewed the literature and rated the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Finally, the panel weighted the evidence and formulated the clinical recommendations. Based on the limited available literature and the corresponding quality of evidence according to GRADE, the guideline panel gave the following recommendations: ↓ Subtotal hysterectomy should only be preferred over total hysterectomy after careful consideration because there are documented disadvantages such as persistent cyclic vaginal bleeding (⊕ΟΟΟ). ↑ Consider vaginal hysterectomy rather than conventional laparoscopic hysterectomy for non-prolapsed uteri when feasible (⊕ΟΟΟ). ↓ Robot-assisted laparoscopic hysterectomy should only be preferred over conventional laparoscopic hysterectomy after careful consideration because the beneficial effect is uncertain and because of the longer operating time (⊕⊕ΟΟ). ↑ Consider concomitant bilateral salpingectomy at the time of hysterectomy if the procedure is not considered to increase the risk of complications significantly (⊕ΟΟΟ). ↑ Consider vaginal vault suspension to the cardinal and the uterosacral ligaments when performing hysterectomy for non-prolapsed uteri (⊕ΟΟΟ). Though supporting evidence is missing, the guideline panel emphasizes that it is good practice not to morcellate uteri with presumed fibroids inside the peritoneal cavity (√). The recommendations serve as professional advice in specific clinical situations. The implementation of the guideline in Denmark will be monitored through the national Danish Hysterectomy and Hysteroscopy Database.

Adjustable mini-sling compared with conventional mid-urethral slings in women with urinary incontinence. A randomized controlled trial.

INTRODUCTION: The primary aim of this study was to compare the objective and subjective outcomes and short-term complication rates of an adjustable single-incision mini-sling (SIMS) vs. standard mid-urethral slings (SMUS). The secondary aim was to report pain perception and complications at the one-year follow up. MATERIAL AND METHODS: The study was designed as a multicenter prospective randomized trial where women were included from eight centers in Denmark, Norway and Sweden. The trial was registered at ClinicalTrials.gov: NCT01754558. A total of 305 women less than 60 years old with verified stress urinary incontinence were included. All women were randomized to SIMS (Ajust® ; n = 155) or SMUS (TVT, TVT-O or TOT; n = 150) and were evaluated by stress test and bladder diary before and after surgery and symptoms related to incontinence using ICIQ-SF, PISQ-12 and PGI-S and PGI-I. Objective cure was defined as no leakage during a stress test and subjective cure defined as no leakage stated in the bladder diary or no indication of urinary leakage in the ICIQ-SF. Furthermore, mesh exposure and dyspareunia were recorded. RESULTS: In total, 280 women [141 (91%) in the SIMS and 139 (94%) in the SMUS groups] participated in the one-year follow up. No difference between the groups was observed regarding objective and subjective outcomes. VAS score disclosed a lower postoperative pain perception in the SIMS group than in the SMUS group. CONCLUSIONS: Ajust® appears to be as efficient as SMUS regarding objective and subjective outcomes and was associated with less pain perception during the postoperative period.

Surgery versus conservative management of endometriomas in subfertile women. A systematic review.

INTRODUCTION: Endometriomas are present in up to 44% of all women with endometriosis and have a detrimental effect on fertility. However, it is controversial whether endometriomas should be surgically removed before assisted reproduction technology. Our purpose was to evaluate whether surgical stripping of endometriomas in subfertile women improves the chance of a live birth. Secondary outcomes were impact on ovarian reserve and pain. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis with results reported in accordance to the PRISMA guidelines. A summary of findings table was developed using GRADE. We searched Medline and Embase. Two reviewers performed the screening. RESULTS: Of 686 manuscripts, we included one randomized controlled trial and nine retrospective cohort studies, mostly of low quality. The odds ratio for live birth after surgery [compared with conservative management before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)] was 0.87 (95% CI 0.64-1.18, six studies, I2  = 3%; ⨁◯◯◯, VERY LOW quality). The mean difference of antral follicle count was -2.09 (95% CI -4.84 to 0.67, four studies). No difference was observed regarding antral follicle count between the two groups (MD -2.09, 95% CI -4.84 to 0.67, four studies, ⨁◯◯◯, VERY LOW quality). Pain outcome was not reported in the included studies. CONCLUSION: The very low quality evidence suggests no difference in odds ratio of live birth between women who underwent surgery for endometriomas before IVF/ICSI compared with conservative management. Further high quality studies are needed, but due to a lack of convincing evidence favoring surgery, we recommend considering conservative treatment if the only indication is subfertility.

Progesterone resistance in endometriosis: origins, consequences and interventions.

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment.