Sonographic Signs of Adenomyosis in Women with Endometriosis Are Associated with Infertility.

We compared the prevalence of ultrasound signs of adenomyosis in women with endometriosis who underwent surgery to those who were managed conservatively. This was a retrospective study of women evaluated at a tertiary endometriosis referral center who underwent 2D/3D transvaginal ultrasound. Adenomyosis diagnosis was based on the presence of at least three sonographic signs. The study group subsequently underwent laparoscopic surgery while the control group continued conservative management. Statistical analysis compared the two groups for demographics, symptoms, clinical data, and sonographic findings. The study and control groups included 244 and 158 women, respectively. The presence of any, 3+, or 5+ sonographic signs of adenomyosis was significantly more prevalent in the study group (OR = 1.93-2.7, p < 0.004, 95% CI; 1.24-4.09). After controlling for age, for all findings but linear striations, the OR for having a specific feature was higher in the study group. Women in the study group with ≥ 5 sonographic signs of adenomyosis had more than twice the risk of experiencing infertility (OR = 2.31, p = 0.012, 95% CI; 1.20-4.45). Sonographic signs of adenomyosis are more prevalent in women with symptomatic endometriosis who underwent surgery compared with those who continued conservative management. Women with 5+ findings have a significantly increased risk of infertility. Adenomyosis on ultrasound should be considered in the management decisions regarding these patients.

The expected cumulative incidence of live birth for patients starting IVF treatment at age 41 years or older.

RESEARCH QUESTION: What is the cumulative incidence of live birth (CILB) for high-order consecutive IVF cycles, and which factors are associated with live birth in women aged ≥41 years using autologous oocytes? DESIGN: A retrospective cohort study including 146 patients aged 41 years to <44 years who started their first IVF cycle attempt using autologous oocytes, between January 2006 and December 2013. RESULTS: After 13 IVF cycles, CILB reached up to 33.6%. After six IVF cycles, 42 (28.8%) women delivered a live infant (85.7% of the total live birth). Mean live birth rate per cycle declined with age at the initial cycle (8% at 41 years; 5.8% at 42 years; and 4.1% at 43 years). Multivariable modified Poisson regression models identified patient's age (RR for 41 years versus 43 years: 0.47; 95% CI 0.25 to 0.87; P = 0.01), smoking status (RR 0.21; 95% CI 0.05 to 0.08; P = 0.02), and mean number of fertilized oocytes (RR 1.23; 95% CI 1.08 to 1.39; P < 0.01) as factors significantly associated with the probability of a live birth. CONCLUSIONS: Multiple repeat IVF cycles in women aged 41-44 years offers a reasonable long-term success rate. After six cycles of treatment, about 29% of women of advanced reproductive age using autologous oocytes expected to achieve a live birth. This information might assist in fertility counselling and managing patients' expectations by adjusting the appropriate treatment strategy and number of IVF cycle attempts, especially in countries in which egg donation is prohibited or when multiple repeated IVF cycles attempts are financially affordable.

Sonographic Signs of Adenomyosis Are Prevalent in Women Undergoing Surgery for Endometriosis and May Suggest a Higher Risk of Infertility.

OBJECTIVES: To determine the prevalence of ultrasound features suggestive of adenomyosis in women undergoing surgery for endometriosis compared with a control group of healthy women without endometriosis. METHODS: Retrospective case-control study comparing women with intractable pain or infertility, who underwent transvaginal ultrasound and subsequent laparoscopic surgery, with a control group of healthy women without a previous history of endometriosis. A diagnosis of adenomyosis on TVUS was made based on asymmetrical myometrial thickening, linear striations, myometrial cysts, hyperechoic islands, irregular endometrial-myometrial junction, parallel shadowing, and localized adenomyomas and analyzed for one sign and for three or more signs. RESULTS: The study and control groups included 94 and 60 women, respectively. In the study group, women were younger and had more dysmenorrhea and infertility symptoms. The presence of any sonographic feature of adenomyosis, as well as three or more signs, was found to be more prevalent in the study group, which persisted after controlling for age, for all features but linear striations. Women in the study group who had five or more sonographic features of adenomyosis had more than a threefold risk of suffering from infertility (OR = 3.19, p = 0.015, 95% CI; 1.25-8.17). There was no association with disease severity at surgery. CONCLUSIONS: Sonographic features of adenomyosis are more prevalent in women undergoing surgery for endometriosis compared to healthy controls. Women with more than five features had an increased risk of infertility.

The Clinical Significance of Endocannabinoids in Endometriosis Pain Management.

Introduction: Patients with endometriosis often suffer from diffuse and poorly localized severe pain. The current pain management strategies include medical and hormonal therapy, as well as surgery. Medical management of pain is often insufficient and is associated with high rate of recurrence. Better pain management is therefore of urgent need. Methods: Among the various candidates, the endocannabinoid system (ECS) has recently emerged as a relevant pharmacological target for the management of endometriosis-related pain. A computerized literature search was performed to identify relevant studies combining the keywords "endometriosis," "endocannabinoid," "cannabinoid receptor," "THC," and "pain mechanisms." Conclusions: This review describes the multiple and complex pain mechanisms associated with endometriosis. Current data and theories concerning the link between the ECS and pain management for endometriosis patients are presented. Finally, we will discuss which aspects of endometriosis-associated pain can be targeted by modulation of the ECS.

Laparoscopic Findings Associated with Bladder Endometriosis Are Correlated with Disease Severity.

STUDY OBJECTIVE: Bladder involvement is rare in endometriosis. The prevalence is estimated to be ∼1% in patients with endometriosis. However, this figure seems to be an underestimation. The diagnosis of bladder endometriosis might be missed during laparoscopy. The aim of this study was to determine an intraoperative visual score of pelvic lesions that help the surgeon suspect bladder endometriosis. Design, Design Classification: A retrospective analysis was performed on the intraoperative photographs and videos of 69 patients with histological confirmation of bladder endometriosis. SETTING: A tertiary referral center. PATIENTS: Sixty-nine patients with bladder endometriosis were operated on in our center over a 9-year period. INTERVENTIONS: Evaluation and analysis of intraoperative laparoscopic findings. MAIN RESULTS: We found three subtypes of laparoscopic findings that can assist with diagnosing bladder endometriosis. The most prominent sign was named "kissing round ligaments" (Type K), in which the right and left round ligaments appear closer to each other than usual or even touching one another. This sign is strongly associated with full-thickness invasion of the bladder. Other laparoscopic findings that indicated bladder endometriosis were anatomical distortion (Type A) and proximal occlusion of the tubes (Type B). We further define a scoring system for the lesion that correlates with the severity of the bladder endometriosis from superficial lesions to full thickness. CONCLUSION: Bladder endometriosis is a rare condition and often remains undiagnosed. Indeed, even during surgery, bladder endometriosis can be missed if the operator is not aware of the suggestive signs. Operative laparoscopic findings may help the surgeon to diagnose bladder endometriosis, and these signs correlate with the severity of the disease.

Fertility outcome of laparoscopic treatment in patients with severe endometriosis and repeated in vitro fertilization failures.

OBJECTIVE: To evaluate fertility outcomes in infertile women with severe endometriosis (The revised American Fertility Society classification [AFS] 3-4) and repeated IVF failures, who underwent surgery due to exacerbation of endometriosis-related symptoms. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): All women who failed IVF treatment before surgery and who underwent laparoscopic surgery for severe endometriosis between January 2006 and December 2014. INTERVENTION(S): All patients were operated by highly skilled surgeons specializing in laparoscopic surgery for advanced endometriosis. Only patients with evidence of endometriosis in the pathology specimens were included in this study. MAIN OUTCOME MEASURE(S): Delivery rate after surgery. RESULT(S): Seventy-eight women were included in the present study. All women were diagnosed with severe endometriosis during surgery (AFS 3-4) and all women had experienced failed IVF treatments before surgery. All women were symptomatic before their surgery. After surgical treatment 33 women (42.3%) delivered. Three women (9%) conceived spontaneously and all other women conceived after IVF treatment. Women who delivered were younger (32.5 [±4.1] years vs. 35.5 [±3.8] years), were less often diagnosed with diminished ovarian reserve before surgery (6% vs. 28.8%), and were more often diagnosed with normal uterine anatomy (by preoperative transvaginal ultrasound and during operation). In addition, performing salpingectomy during surgery was associated with a trend of improvement in delivery rates after surgery (70% in women who delivered vs. 51% in women who failed to deliver). CONCLUSION(S): Symptomatic women with severe endometriosis and repeated IVF implantation failures may benefit from extensive laparoscopic surgery when performed by an experienced multidisciplinary surgical team to improve IVF outcome.

Surgery versus pharmacological treatment for endometriosis.

The two major consequences of endometriosis are pain and infertility. Despite numerous studies and proposed guidelines, some aspects of the treatment for these complications are still under debate or lack convincing evidence that favors one approach over the other. Future studies will hopefully present new evidence in regard to the optimal treatment for each indication and suggest innovative pharmacotherapy following improved understanding of the pathophysiology of endometriosis. Until then, individualization of the treatment according to the specific indication, taking into consideration the benefits versus the risks for the patient and the tolerability profile, remains the most appropriate approach.

Vaginal mifepristone for the treatment of symptomatic uterine leiomyomata: an open-label study.

OBJECTIVE: To evaluate the efficacy and safety of 3 months of vaginal mifepristone treatment on leiomyoma volume and related symptoms. DESIGN: Prospective, open-label, two tertiary centers, phase II clinical trial. SETTING: Two tertiary medical centers in Israel. PATIENT(S): Thirty-three enrolled women, ages 30-53 years, diagnosed with symptomatic uterine fibroids. INTERVENTION(S): Patients received 10 mg mifepristone vaginally daily for 3 months. MAIN OUTCOME MEASURE(S): Reduction in uterine leiomyoma volume. Improvement in symptoms related to uterine fibroids was assessed with the use of the "Uterine Fibroid Symptoms Quality of Life Questionnaire" (UFS-QoL). The number of bleeding days, safety, and tolerability were secondary measures. RESULT(S): Mifepristone treatment significantly reduced leiomyoma volume from 135.3 ± 22.9 cc at enrollment to 101.2 ± 22.4 cc after 3 months of treatment. The UFS-QoL Score significantly decreased from 20.7 ± 0.7 at enrollment to 14.0 ± 0.8 after 3 months of treatment. The number of bleeding days significantly decreased by 3.5 days. Endometrial biopsies showed no evidence of endometrial hyperplasia or cellular atypia. There were no major side effects during the course of the study, and treatment was well tolerated. CONCLUSION(S): Vaginal mifepristone may offer an effective treatment option for women with symptomatic uterine leiomyoma and can improve the patients' quality of life. CLINICAL TRIAL REGISTRATION NUMBER: NCT00881140.

Long-term follow-up after ureteral reimplantation in patients with severe deep infiltrating endometriosis.

OBJECTIVE: To investigate the intraoperative features and long-term postoperative results of patients with ureteral endometriosis who underwent ureteral reimplantation. STUDY DESIGN: In this retrospective study, we reviewed records of all patients with ureteral endometriosis treated by ureteral reimplantation. Pre-, intra- and post-operative information was collected. RESULTS: Of patients operated for endometriosis, seven were diagnosed with severe ureteral endometriosis and underwent ureteral reimplantation. Psoas hitch was the preferred technique for the ureteral reimplantation. During a mean postoperative follow up of 42.3 ± 20.0 months, all but one patient reported significant symptomatic improvement. None of the patients needed additional medical or surgical treatment and no recurrence was noted. CONCLUSION: Ureteral reimplantation performed by a multidisciplinary surgical team is a suitable technique in selected cases, gives good long-term results and has no need for repeated surgical treatment.

Deep endometriosis inflicting the bladder: long-term outcomes of surgical management.

OBJECTIVE: To assess the efficacy and safety of laparoscopic treatment of bladder endometriosis, especially in cases of full thickness endometriotic nodules. DESIGN: Retrospective review of medical records. SETTING: Tertiary medical center and a referral center for endometriosis. POPULATION: Sixty-nine patients with bladder endometriosis that underwent surgery between January 2005 and December 2011. METHODS: The records of all patients with bladder endometriosis were reviewed and the pre-, intra- and postoperative information of patients who underwent surgery was collected. MAIN OUTCOME MEASURES: Efficacy, safety and long-term outcome of laparoscopic treatment of bladder endometriosis. RESULTS: The mean age of 69 patients with bladder endometriosis was 31.3 ± 4.6 years. Preoperative urinary symptoms (such as frequency, urgency, dysuria and others) were present in 28 (40.0%) patients. Laparoscopy was performed in all patients. Deep detrusor involvement was found in 45 (65.2%) patients. Of these, 21 patients underwent partial cystectomy due to a full thickness lesion. Deep nodule resection without bladder invasion was performed in 24 (34.8%) patients and bladder nodule coagulation and ablation in the remaining 24 (34.8%) patients with superficial involvement. No intraoperative complications were noted. Postoperative follow-up results were available for all patients. After a median (range) follow-up period of 60 (4-92) months, 92.7% of the patients were asymptomatic or reported improvement in symptoms. CONCLUSIONS: After a long-term follow-up surgical management of bladder endometriosis is strongly recommended. During surgery, careful inspection and full excision of bladder lesions should be performed. Laparoscopic excision is a safe and efficacies approach.

Intradermal sex hormone desensitization for relief of premenstrual symptoms may improve the obstetric outcome of women with recurrent pregnancy loss.

The aim of this study was to determine whether women with recurrent pregnancy loss (RPL) and concurrent premenstrual syndrome (PMS) who underwent desensitization with sex hormones had an improved obstetric outcome. This manuscript summarizes a 10 year open label prospective follow up study of 26 women with RPL, aged 25-42 with 3-8 previous miscarriages and PMS, who had hormone hypersensitivity on skin testing. Skin testing was positive to estradiol in 23 women, progesterone in 20 women and to both estrogen and progesterone in 17 women. Amelioration of the symptoms of PMS (according to the VAS) was seen in 21 of 26 patients after desensitization with small doses of sex hormones intradermally. There was long term and stable reduction of severe PMS in 21 of 26 patients after desensitization. Five women conceived after skin testing, prior to desensitization. Sixteen of 26 women (61%) had subsequent live births. Five women had two subsequent live births in the subsequent pregnancy. There were no obstetric complications. Five women had two subsequent pregnancies with live births. It seems that correction of sex hormone hypersensitivity was accompanied by relief of persistent PMS, may have a positive effect on the chances of a successful pregnancy.

Thoracic endometriosis syndrome is strongly associated with severe pelvic endometriosis and infertility.

STUDY OBJECTIVE: To evaluate the clinical and surgical features of thoracic endometriosis syndrome (TES) represented by catamenial pneumothorax and pelvic endometriosis and to describe their association with infertility. DESIGN: Retrospective clinical study (Canadian Task Force classification: II-2). SETTING: Academic tertiary referral endometriosis center. PATIENTS: Seven patients who had undergone surgery because of thoracic and pelvic endometriosis between 2004 and 2010. INTERVENTIONS: Thoracic and pelvic exploration and treatment and fertility treatment. MEASUREMENTS AND MAIN RESULTS: Concurrently, thoracic and pelvic endometriosis, and subsequent fertility were determined during long-term follow-up after combined surgical and pharmacologic interventions. The most frequent thoracic finding was diaphragmatic implants. Except for 1 patient with recurrent pleurodesis at 1 month after video-assisted thoracoscopy, no patients experienced recurrence of thoracic symptoms during a median (range) follow-up of 31.4 (1-61) months. Severe pelvic endometriosis was diagnosed in 6 patients with notable urologic and gastrointestinal tract involvement. Only 1 patient with catamenial pneumothorax had no macroscopic pelvic lesions. There was a considerable delay between the onset of pelvic symptoms and diagnosis. Median postoperative follow-up was 31.5 (7-84) months. Most patients who tried to conceive had primary infertility. CONCLUSION: Thoracic endometriosis syndrome, represented by catamenial pneumothorax, was strongly associated with severe pelvic endometriosis and a high rate of infertility. Inasmuch as many patients with thoracic endometriosis syndrome are treated by thoracic surgeons using video-assisted thoracoscopy, it is desirable to involve an experienced gynecologist who can diagnose and treat concurrent pelvic endometriosis.

Multidisciplinary team approach to management of severe endometriosis affecting the ureter: long-term outcome data and treatment algorithm.

STUDY OBJECTIVE: To examine the efficiency of laparoscopic ureterolysis for ureteral endometriosis and to describe appropriate treatment. DESIGN: Prospective trial (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Forty-five patients who underwent surgery to treat ureteral endometriosis between 2005 and 2009. INTERVENTION: Laparoscopic ureteral ureterolysis. MEASUREMENTS AND MAIN RESULTS: Long-term follow up of symptoms, urinary tract anatomy and function, and the need for further intervention were performed. Ureteral endometriosis was observed in 14.2% of 315 patients with endometriosis. Of the 45 study patients, 95.5% had dysmenorrhea, 60% had dyspareunia, and 45% were infertile. Half of the patients had previously undergone laparoscopic procedures. Urinary tract symptoms were present in 15.9% of patients. Preoperative hydronephrosis or hydroureter was observed in 10 patients (22.2%), and impaired urinary function in 2 patients (4.4%). Laparoscopy demonstrated left ureteral involvement in 82.2% of patients, and deep infiltrative endometriosis in 80%. Laparoscopic ureterolysis was feasible in 91.1% of patients. In 4 patients, ureterolysis was not feasible, and primary reimplantation of the ureter was performed. Forty-one patients (91.1%) had no symptoms or had marked improvement postoperatively and required no further treatment. Two patients (4.8%) underwent repeat surgery. In 80% of patients with hydroureteronephrosis, the postoperative sonogram was normal. CONCLUSIONS: Ureteral endometriosis can be treated effectively using laparoscopic ureterolysis in almost all patients. Different treatment approaches should be based on the results of preoperative evaluation and operative findings by a multidisciplinary team. Urinary assessment is crucial because most patients demonstrate no urinary tract symptoms and initial renal investigation can prevent irreversible damage.

Steroid hormone hypersensitivity: clinical presentation and management.

Hypersensitivity to estrogens and progestogens is often undiagnosed. The condition has many manifestations, including premenstrual syndrome, dysmenorrhea, and impaired fertility. Diagnosis is confirmed by skin testing for inflammatory responses to small doses of the hormone, and desensitization with small doses of the hormone is the most appropriate form of management.

Measurement of electrical resistance of dermal-visceral zones as a diagnostic tool for gynecologic disorders.

BACKGROUND: Non-invasive screening tests may allow early diagnosis and prompt treatment, thereby potentially reducing morbidity and mortality and reducing costs for the community. This may be especially important for gynecologic pathologies that are difficult to promptly diagnose, such as endometriosis or ovarian cancer. OBJECTIVES: To evaluate the reliability of measuring skin resistance using the Medex Test for screening and diagnosis of gynecologic pathologies in a blinded single-center study. METHODS: We enrolled 150 patients: 59 with a functional disorder and 91 with an organic disease. Measurements were carried out in all patients and the results were analyzed separately by a second physician who was blinded to the patients' diagnosis. RESULTS: A high correlation was found between the clinical diagnosis and the results of the measurement of electrical skin resistance, with a specificity of 76.3% (45/59) for functional disorders and a sensitivity of 85.7% (78/91) for organic disorders, positive predictive value of 84.8% (78/92) and negative predictive value 77.6% (45/58). The kappa value for the results was 0.622, representing a value much better than expected randomly. CONCLUSIONS: The Medex Test has a good specificity and a high sensitivity for the diagnosis of gynecologic disorders. Further prospective studies are needed to validate these preliminary findings.

A prospective follow-up of two 21/7 cycles followed by two extended regimen 84/7 cycles with contraceptive pills containing ethinyl estradiol and drospirenone.

BACKGROUND: Continuous use of combined oral contraceptives is currently attracting growing interest as a means of improving menstrual related symptoms and reducing the number of bleeding days. OBJECTIVES: To evaluate bleeding patterns, menstrual symptoms and quality of life with an extended 84/7 oral contraceptive regimen versus 21/7 cycles. METHODS: In two consecutive run-in cycles, 30 microg ethinyl estradiol and 3 mg drospirenone tablets taken on days 1-21 were followed by a tablet-free period from days 22 to 28 of each cycle and then by two 84 day cycles of pill use with a 7 day tablet-free interval. The primary outcome was the total number of bleeding/spotting days. Secondary outcomes were severity of daily symptoms, general well-being determined by the PGWBI questionnaire, and overall treatment satisfaction. RESULTS: Of the 137 women invited to participate in the study 109 (aged 18-40 years) were enrolled. The number of bleeding days decreased by about one-third from a calculated 31.8 days of bleeding under a cyclic 21/7 regimen to an expected total of 21.8 days for the extended 84/7 regimen. The incidence of menorrhagia, intermenstrual bleeding, dysmenorrhea, abdominal bloating, breast tenderness, depressive moods and irritability - when compared at enrollment and at the end of the second extended study period--was significantly lower (P < 0.005) among women on the continuous pill regimen. The median (range) global PGWBI scores were not substantially different before and after the extended use cycles: 78.2 (39.1-96.4) and 77.3 (30.9-96.4), respectively. Body weight and skin condition also remained constant. At the completion of the study: 65.5% of the women were either highly satisfied (41.4%) or satisfied (24.1%) with the extended regimen. CONCLUSIONS: The extended 84/7 regimen was found to be satisfactory for the majority of participants and was associated with a decrease in the number of bleeding days and an improvement in menstrual symptoms compared to 21/7 cycles.

Long-term outcome after laparoscopic treatment of heterotopic pregnancy: 19 cases.

STUDY OBJECTIVE: To determine the long-term outcome of intrauterine pregnancies after treatment of heterotopic pregnancies. DESIGN: Retrospective cohort study (Canadian Task Force classification II-3). SETTING: Tertiary center university hospital. PATIENTS: All women who underwent surgery because of heterotopic pregnancy over 12 years. INTERVENTION: Laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: Infant development and future pregnancy. Extrauterine pregnancies were located in the tube (n = 13), uterine cornua (n = 3), ovary (n = 1), and tubal stump (n = 2). During laparoscopy, a ruptured tube was found in 6 tubal pregnancies (46%), blood transfusion was needed in 7 heterotopic pregnancies (37%), and salpingectomy was performed in 12 women with tubal pregnancies (91.7%). The pregnancy outcome consisted of 13 babies (term and preterm) taken home and 5 miscarriages. Long-term follow up demonstrated that 10 of 13 infants (76.9%) exhibited normal development. Three infants, all from 1 triplet pregnancy, exhibited borderline to normal development. Ten of 15 women achieved additional pregnancies, with 10 deliveries and only 1 extrauterine pregnancy in the tubal stump. CONCLUSIONS: Women with a heterotopic pregnancy are at high risk for late diagnosis and at risk for hypovolemic shock at diagnosis, and may require blood transfusion. The outcome of intrauterine pregnancy in association with heterotopic pregnancy requiring surgical intervention is good, and most complications were associated with multifetal pregnancy and preterm delivery.

Emergency laparoscopy for suspected ovarian torsion: are we too hasty to operate?

OBJECTIVE: To reevaluate the rate of correct diagnosis of ovarian torsion (OT) in our department. DESIGN: Retrospective computerized chart review. SETTING: Tertiary referral center. PATIENT(S): Seventy-eight women who underwent laparoscopy for suspected OT. INTERVENTION(S): Laparoscopy. MAIN OUTCOME MEASURE(S): Rate of true diagnosis of torsion, correlation with Doppler studies. RESULT(S): The preoperative diagnosis of OT was confirmed in only 36 (46.1%) of the patients. Immediate operation (<10 hours) after admission (n = 48) was associated with a statistically significantly higher likelihood of operatively confirming OT (56.2% vs. 28.6%). We found that the lack of ovarian blood flow on Doppler sonography was a good predictor of OT; women with pathologic flow were statistically significantly more likely to have OT (77% vs. 29%). The sensitivity and specificity of abnormal ovarian flow for OT were 43.8% and 91.7%, respectively, with a positive and negative predictive value of 78% and 71%, respectively. CONCLUSION(S): Despite 20 years of research, the accuracy of the preoperative diagnosis of OT remains low. The urge to operate can be attributed to the importance of preserving ovarian function in young women as well as to the availability and the low associated complication rate of laparoscopy.

Estradiol valerate as a possible endocrine reproductive disruptor: evidence from an in vivo rat model.

We used an in vivo rat model to demonstrate that low-dose intradermal exposure to E(2) valerate has an inverse effect on the female's estrus cycle pattern and can significantly reduce litter size. These results suggest that, under certain circumstances, environmental exposure to exogenous estrogens may play a role as an endocrine disruptor and adversely affect reproductive outcome.

Recurrent pregnancy loss and inappropriate local immune response to sex hormones.

PROBLEM: The cause of recurrent miscarriage is often unknown. Recurrent miscarriage may be associated with inappropriate responses to progesterone and estrogen. We examined whether the condition may be diagnosed by skin testing. METHOD OF STUDY: In a longitudinal prospective study, the weal and flare reaction after intradermal injection of estradiol and progesterone was compared in 29 women with recurrent miscarriage to the response in 10 healthy women. Reactions were evaluated after 20 min, 24, and 48 hr and 5 days later. RESULTS: Estrogen hypersensitivity was found in 23 patients, and progesterone hypersensitivity in 20 patients. No patient in the control group demonstrated sex hormone hypersensitivity. CONCLUSION: Recurrent pregnancy loss may be associated with inappropriate local immune responses to sex hormones. Further research is necessary into the mechanisms of hypersensitivity to estrogen and progesterone and their interactions with other systems.