Spontaneous haemoperitoneum in pregnancy and endometriosis: a case series.

OBJECTIVE: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in pregnancy) and the association with endometriosis. DESIGN: Retrospective case note review. SETTING: Dutch referral hospitals for endometriosis. SAMPLE: Eleven women presenting with 15 events of SHiP. METHODS: In collaboration with the Dutch Working Group on Endometriosis, unpublished cases of SHiP that occurred in the Netherlands between 2010 and 2015 were retrieved. MAIN OUTCOME MEASURES: Maternal and perinatal mortality and morbidity. RESULTS: SHiP occurred predominantly in the second and third trimester of pregnancy. The earliest and major presenting symptom was an acute onset of abdominal pain, often combined with low haemoglobin levels or signs of fetal distress. Imaging was a diagnostic tool when free peritoneal fluid could be observed. For surgical treatment of the bleeding site, a midline laparotomy was mostly needed, the median estimated amount of blood loss was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a certain moment in time and therefore was probably involved in the pathogenesis of SHiP. Four women showed recurrence of SHiP. In one of these cases the second event of SHiP occurred in a subsequent pregnancy. CONCLUSION: Pregnancy outcomes of SHiP are improving when compared with previous reports, with absent fetomaternal and perinatal mortality in this recent series. Growing knowledge and adequate multidisciplinary intervention may have contributed to these favourable results. Increasing awareness of this serious complication of pregnancy is advocated, especially in women diagnosed with endometriosis. TWEETABLE ABSTRACT: Growing awareness of SHiP is advocated, especially in women diagnosed with endometriosis.

Biochemical characterization of peritoneal fluid in women during the menstrual cycle.

Peritoneal fluid was collected at laparoscopy in women during the menstrual cycle and was assayed for protein and steroid hormone content. The total protein concentration in peritoneal fluid and the concentrations of the steroid hormone-binding proteins, transcortin and sex hormone-binding globulin, the polypeptide hormones, LH, FSH, and PRL, correlated with the plasma concentration but were lower; they were, respectively, 68%, 71%, 68%, 42%, and 34% of the plasma concentration. The concentrations of steroid hormones secreted by the ovary, i.e. 17 beta-estradiol, progesterone, androstenedione, and testosterone, were always equal or higher in peritoneal fluid than in plasma. In contrast, the concentrations of cortisol, a nonovarian steroid hormone, was 40% lower in peritoneal fluid than in plasma. No cyclic variations were observed in the peritoneal fluid concentrations of androstenedione and testosterone, two steroid hormones secreted by the stromal component of the ovary. On the contrary, the concentrations of 17 beta-estradiol and progesterone secreted by the follicular apparatus of the ovary increased sharply in peritoneal fluid after ovulation, reaching values of 44000 pg/ml and 3000 ng/ml, respectively. They declined progressively, whereas in plasma, peak concentrations were achieved only in the midluteal phase. In conclusion, the concentrations of 17 beta-estradiol and progesterone are much higher in peritoneal fluid than in plasma for at least 1 week after ovulation. We suggest that the secretion of the early, not yet vascularized, corpus luteum is directed preferentially toward the peritoneal cavity, creating a specific hormonal environment for the released oocyte and the oviduct.

The "gonadotropin-resistant ovary" syndrome as a cause of secondary amenorrhea and infertility.

A patient with secondary amenorrhea with the gonadotropin-resistant ovary syndrome is described. The physiopathology of the syndrome is investigated and discussed. Ovulation could not be induced by using very high doses of gonadotropins. The presence of a hormone abnormality or of an inhibitor preventing hormone action could not be substantiated. It is suggested that the disease may be due to an autoimmune reaction with antibody formation against the receptor sites for gonadotropins.

The endoscopic localization of endometrial implants in the ovarian chocolate cyst.

OBJECTIVE: To describe the characteristics of the endometrial cyst and to locate the implants for selective biopsy. DESIGN: Prospective study. SUBJECTS: Fifty-one women with one or two ovarian chocolate cysts of 3 cm or more were investigated. INTERVENTIONS: Laparoscopy and random biopsy versus a new technique of ovarioscopy and selective biopsy. MAIN OUTCOME MEASURE: Visual characteristics and histopathology of endometrial cysts. RESULTS: The clinical suspicion of an endometrioma was confirmed in a series of 59 hemorrhagic cysts by histopathology in 89% and 42%, respectively, of typical and atypical cases and in 27% of recurrent chocolate cysts in the presence of postoperative adhesions. The atraumatic technique of ovarioscopy allowed description of the typical characteristics of the inner wall of the endometrioma and location of the active implants for biopsy. Endometrial tissue was obtained by small ovarioscopy-guided biopsies in 82% of the cases versus 42% in large random biopsies. Red lesions were highly significant for a mucosa-type implant and were predominantly located at the site of invagination stigma and adhesions with the pelvic wall. CONCLUSIONS: Endoscopy of ovarian chocolate cysts allows observation of typical features of the wall that differentiates it from other benign cysts of the ovary. Microbiopsies obtained under endo-ovarian endoscopy provided significantly more active, endometrial tissue than random biopsies. The data confirm that in most cases the endometrioma is formed by invagination of the cortex and that active implants are located at the site of invagination. Ovarioscopy is therefore proposed as a useful tool to differentiate in doubtful cases between a hemorrhagic functional and an endometriotic cyst and to select the sites for biopsies.

Peritoneal endometriosis: scanning electron microscopy and histology of minimal pelvic endometriotic lesions.

In 36 patients with laparoscopically diagnosed endometriosis, biopsies were taken from different areas of the pelvic peritoneum bearing foci of endometriosis. The biopsies were studied by scanning electron microscopy and by light microscopy. Combined use of these techniques resulted in the differentiation of three topographically and morphologically different types of endometriotic lesions: intraperitoneal endometriotic polyps with no glandular openings but associated with deeper endometriotic glands and stroma; intraperitoneal endometriotic foci with surface epithelium, glands, and stroma; and retroperitoneal small lesions with few glands and scant stroma. The morphologic features of endometriotic foci indicate that they do not follow the typical cyclic changes described for the uterine endometrium. Our microanatomic characterization of endometriosis is discussed in relation to the conflicting data concerning peritoneal fluid constituents and infertility in patients with minimal endometriotic lesions.

Reconstruction of the ovary containing large endometriomas by an extraovarian endosurgical technique.

OBJECTIVE: To describe and evaluate the surgical treatment of large ovarian endometriomas by an extraovarian endosurgical technique. DESIGN: Prospective case series study. SETTING: University center and tertiary referral center for endoscopic surgery. PATIENTS: Patients with large ovarian endometriomas. INTERVENTION: A two-step endosurgical procedure: the first step is a combined diagnostic and operative procedure confirming the diagnosis and preparing the involution of the pseudocyst and the second step includes adhesiolysis and superficial coagulation of the inverted cortex. MAIN OUTCOME MEASURES: Operative findings and recurrence of endometriomas in the operated ovaries. RESULTS: Sixteen patients presenting with 20 large typical ovarian endometriomas were operated using the two-step endosurgical technique. Both steps were performed on 18 endometriomas. One patient with bilateral endometriomas refused the second endoscopic procedure. The long-term follow-up showed no recurrence in the 18 ovaries that were treated by the two-step endoscopic technique. CONCLUSIONS: The two-step extraovarian endosurgical technique can be applied in large typical endometriomas to reconstruct the ovary without excision and is followed by a low recurrence rate.

The staging of peritoneal endometriosis by the type of active lesion in addition to the revised American Fertility Society classification.

OBJECTIVE: To evaluate changes in peritoneal endometriosis by the type of lesion in comparison with the scoring system of the revised American Fertility Society (AFS) classification. DESIGN: Prospective evaluation at laparoscopy before and 6 months after discontinuance of a 3-month medical therapy with either dydrogesterone or danazol. SETTING: A general hospital. PATIENTS: Forty cycling women with endometriosis and infertility. Fourteen patients could be fully evaluated by their revised AFS score and type of peritoneal lesion. INTERVENTIONS: Laparoscopy before and 6 months after discontinuance of medical therapy. MAIN OUTCOME MEASURE: Revised AFS score and type of peritoneal lesions. RESULTS: The revised AFS score decreased or remained unchanged in 13 of 14 patients, whereas red papular or vesicular lesions were present at both laparoscopies in 5, absent in 4, disappeared in 3, and appeared de novo in 2. A changing pattern also was seen in other types of small peritoneal lesions. CONCLUSION: In contrast with the revised AFS score, the study of the type of peritoneal lesions shows a changing pattern of activity. The significance in pathophysiological and clinical studies should be investigated further.

Accuracy of endometrial biopsy dating in relation to the midcycle luteinizing hormone peak.

The accuracy of endometrial biopsy dating was evaluated in a selected group of apparently normal women in whom the basal body temperature (BBT), the onset of subsequent menstruation, the midcycle luteinizing hormone (LH) peak, and the 17beta-estradiol peak were determined. Forty-two women with regular cycles, normal ovaries at laparoscopy, and luteal phases of 12 to 15 days were studied. In group I (n=20), the infertility could be explained satisfactorily by either tubal occlusion or infertility of the husband, while in group II (n=22) no explanation was found for the infertility. In group I the duration of the luteal phase, defined as the interval between the LH peak and the onset of subsequent menstruation, was 13.4+/-0.7 days. The plasma 17beta-estradiol concentration declined (P less than 0.01) on the day of the LH peak in both groups of women, while the first significant rise (P less than 0.05) in BBT occurred in groups I and II, respectively, 1 and 2 days following the LH peak. Dating of the endometrial biopsy correlated with the LH peak with standard deviations of 1.2 and 1.3 days, respectively, in groups I and II. It is suggested that, in women with a progressive rise in BBT over several days, the localization of the LH peak can be helpful for correct interpretation of the endometrial biopsy.

Delayed onset of luteinization as a cause of infertility.

Two groups of infertility patients with regular cycles and apparently normal ovarian function were studied. In group I (n = 28) the infertility could be explained satisfactorily either by tubal occlusion or by infertility of the husband, or the women became pregnant within a few months. In group II (n = 32) no explanation was found for the infertility. Significantly fewer ovulation stigmata were present at laparoscopy in group II than in group I (P less than 0.05). In group I the basal body temperature (BBT) (P less than 0.001) and the plasma progesterone concentrations (P less than 0.05) were significantly elevated on the 1st day following the luteinizing hormone (LH) peak. In group II, THE BBT was slightly elevated on the 1st day following the LH peak (P less than 0.05), but the increase in the plasma progesterone concentrations occurred only on the 2nd day following the LH peak. In four women the onset of the BBT rise followed a normal LH peak with delays respectively, of 3, 4, 4, and 5 days, and in two women no LH peak occurred immediately prior to the onset of the BBT rise. The datings of the endometrial biopsies in these patients were in phase with the onset of the BBT rise but not with the LH peak. It is concluded that anovulation with in situ luteinization may be a rather frequent cause of infertility in regularly cycling women. A hypothesis about the mechanism of anovulation with in situ luteinization is proposed.

The evolution of experimentally induced hydrosalpinges in rabbits.

Damage to fallopian tubes caused by hydrosalpinges is a major reason for persisting infertility. We describe the mucosal changes that occur following induction of experimentally induced hydrosalpinges in 25 rabbits. Ampullary biopsies obtained at varying intervals were examined with light microscopy and scanning and transmission electron microscopy. Mucosal folds showed progressive atrophy. The epithelium was flattened. The population of ciliated cells decreased and, finally, deciliation became generalized. The morphology of nonciliated cells changed from an initial high content of granules of secretion to a final stage of vacuolated cytoplasm. Cell desquamation was common.

Fetoscopy-guided fetal endoscopy in a sheep model.

Video-endoscopic surgical treatment of the fetus may, in the future, become an alternative to open fetal operation. Six 95-day-old fetal lambs were examined through intrauterine endoscopy using amnioinfusion and specially designed balloon-tipped cannulas. The fetuses were monitored endoscopically for oxygen saturation, heart rate and temperature throughout the procedure. With a rigid 5 millimeter telescope and a flexible 3 millimeter endoscope, the respiratory and upper gastrointestinal tracts could be examined. No mucosal or other trauma was noted upon completion of the endoscopy; all lambs survived the procedure. While the applications of fetal endosurgery are likely to be similar to those of open fetal operation, fetal endoscopy (looking in the fetus) is a new entity for which clinical relevance (rather than mere feasibility) remains to be demonstrated. This technique, however, could become a valuable research tool to study fetal gastrointestinal and pulmonary physiologic factors in situ.

Reversibility of tubal ring sterilization.

PIP: The reversibility of the Falope ring tubal sterilization technique was assessed in 22 rabbits. The microsurgical technique employed for end-to-end reanastomosis is described. The technique resulted in a patency rate of 96% and a pregnancy rate of 86%. Adhesions were found in only 13% of the cases. The results suggest that the Falope ring sterilization technique has a high probability of reversibility in humans.^ieng

Endometrial vascular features prior to and following exposure to levonorgestrel.

A study of endometrial vasculature, mast cell numbers and tissue levels of tissue plasminogen activator (tPA) prior to and following exposure to levonorgestrel (20 micrograms/day) administered via a vaginal ring was undertaken. Following exposure to levonorgestrel, significantly fewer arterioles were present in the endometrium. During the early secretory phase of the control cycle, a positive correlation was found between mast cell numbers and progesterone levels. Levonorgestrel-exposed biopsies had significantly higher numbers of vessels with endothelial gaps and haemostatic plugs when compared with early secretory endometrium and significantly higher numbers of haemostatic plugs when compared with mid-late secretory endometrium. During the early secretory phase, the numbers of vessels possessing haemostatic plugs positively correlated with the peripheral blood levels of oestradiol and the number of contracted endothelial cells showed a positive correlation with progesterone levels. In mid-late secretory biopsies, the numbers of vessels with contracted endothelial cells were found to correlate negatively with oestradiol levels and the difference in the levels of contracted endothelial cells between the mid-late secretory endometrium and levonorgestrel-exposed endometrium correlated positively with progesterone levels of post-treatment cycles.

THE RATIONALE FOR ENDOCRINE THERAPY.

There are three major types of peritoneal endometriotic implant as distinguished by their laparoscopic and morphological characteristics; the microscopic or epithelial-type plaque, the vesicular and papular type and the fibrotic, nodular type. Fluctuations in hormone levels during the menstrual cycle and throughout hormonal therapy have differential effects on the three types of implant. After only a short period of treatment with gestrinone the active types of peritoneal endometriotic implant exhibit inactivity and involutionary changes. Regressive changes in the implants may explain the abolition of the symptoms.

Clinical significance of the luteinized unruptured follicle syndrome as a cause of infertility.

The luteinized unruptured follicle syndrome (LUF) exists and is cause of infertility. Although the data of the laparoscopic inspection of the ovaries and the corpora lutea and of steroid hormone concentrations in peritoneal fluid constitute strong evidence that the syndrome exists, its role as a cause of infertility is less clear. The only evidence available that the LUF syndrome is a cause of infertility, is the finding that the syndrome occurs statistically more frequently in women with unexplained infertility than in a control group of women. It still has to be proven whether the LUF syndrome occurs repetitively in each cycle and causes infertility, or whether the syndrome occurs intermittently and only reduces the probability of conception. Diagnosis of the syndrome can be made by laparoscopic inspection of the ovaries and by the assay of 17 beta-estradiol and progesterone, in peritoneal fluid between day 14 and 20 of the cycle. The relationship between the LUF syndrome and pelvic endometriosis and luteal phase insufficiency is discussed. We suggest that the LUF syndrome might be the cause of endometriosis thus explaining the statistical association between both syndromes, and the infertility of women with only mild endometriosis. We favor the hypothesis that the LUF syndrome might be caused by stress thus constituting a "psychological infertility" and we suggest that the syndrome could explain the spontaneous cure rate. Therefore, before any therapy can be accepted as the treatment of the LUF syndrome, it should be strictly assessed with adequate controls.

Histology and ultrastructure of human endometriotic tissues treated with dydrogesterone (Duphaston).

The histological and ultrastructural changes of ectopic endometrium were studied during treatment with dydrogesterone (Duphaston) in eighteen infertile patients with laparoscopically confirmed endometriosis. Three types of response to therapy, i.e. no response, moderate and good, are detailed. First, focal secretory transformation of the endometriotic epithelium with decidualization of the ectopic stroma was seen in four patients (no response to therapy). In all other patients, the endometriotic implants were undifferentiated (moderate response to therapy) or revealed morphologic features of involution (good response to therapy). Proliferation of endometriotic cells was not seen during treatment with Duphaston, while total eradication of microscopic implants was never observed. Endometriotic implants with good response to Duphaston therapy demonstrated an enhanced autophagic activity within many epithelial cells. Only two patients conceived during a one-year post-treatment follow-up. Both patients demonstrated a good response to therapy.

Ciliogenesis following salpingostomy of rabbit hydrosalpinges.

Twenty-five artificially induced hydrosalpinges were studied in New Zealand white rabbits. Hydrosalpinges had been created after 2-16 wk occlusion of both the fimbrial end and the ampullary isthmic junction (A.I.J.), using either Ethilon 8/0 or tantalum clips. Their diameters ranged from 4 to 12 mm, being larger in the clipped oviducts. In hydrosalpinges larger than 6 mm diameter, a salpingostomy was done and ampullary biopsies were taken and prepared for scanning electron microscopy, and 1-micron sections and ultrathin sections for transmission electron microscopy. The changes observed were those found in previous work (Vásquez et al., 1981). Post-salpingostomy biopsies were taken from 10 patent oviducts at different intervals of time, ranging from 2 days to 8 wk. Ciliogenesis was observed between the 2nd and 3rd wk after salpingostomy.

Experimental hydrosalpinx and salpingostomy in rabbits.

In 137 oviducts of New Zealand white rabbits different kinds of occlusion techniques were tested to induce hydrosalpinges. In 99 oviducts ligatured or clipped both at the fimbrial end and at the ampullary-isthmic junction 67 hydrosalpinges were achieved, whilst in 34 oviducts ligatured or clipped only at the fimbrial end one hydrosalpinx occurred. Most severe histological changes were seen after double clipping. Ligation of the blood vessels to and from the ampulla of 4 oviducts caused no hydrosalpinx formation. After cuff salpingostomy a higher number of patent oviducts was found than after double-loop salpingostomy.

A model for fetal surgery through intrauterine endoscopy.

Video-endoscopic technology may offer new hope for the future of fetal surgery. Ten time-dated pregnant ewes (95 to 105 days; term, 145 days) were used to develop a model of fetal surgery through intrauterine endoscopy. Special 5-mm ports were designed with short, flexible, balloon-tipped shafts. The cannulas were inserted through purse-stringed hysterostomies. Amnioinfusion of warmed physiological fluid (Hartmann) was used as the work medium. Fetal heart rate and oxygen saturation (pulse oximetry), temperature, and amniotic pressure were monitored continuously through endoscopically placed sensors. Surgical procedures included subcutaneous dissection of the abdominal wall and ligation of the urethra in the male fetus (n = 7), ligation of the urachus within the umbilical cord (n = 8), and endoscopy of the fetal esophagus and trachea (n = 6). Bloodless surgery was achieved with a novel coagulation device that allows bipolar cutting and coagulation in an electrolyte-rich fluid medium. The mean fetal operative time was 147 minutes (range, 130 to 195). The intraamniotic temperature was maintained between 38.0 +/- 0.9 degrees C and 41.7 +/- 1.7 degrees C throughout the procedure. Oxygen saturation ranged from 51 +/- 20% to 72 +/- 14%, and fetal heart rate from 120 to 140 beats per minute. In conclusion, intrauterine endoscopy in a fluid medium allows fully monitored surgical procedures, lasting more than 2 hours, to be performed on the fetal lamb.