Pelvic inflammation induced by diagnostic laparoscopy in baboons.

OBJECTIVE: To test the hypothesis that diagnostic laparoscopy can cause pelviperitoneal inflammation. DESIGN: Retrospective analysis of data collected during a prospective controlled study in baboons. SETTING: An academic research environment. ANIMAL(S): Samples were collected during laparoscopies in female baboons at the Institute of Primate Research, Kenya. INTERVENTION(S): In the first part of the study, 44 laparoscopies were performed in 16 baboons (5 with a normal pelvis, 11 with endometriosis) during the luteal phase, with a time interval of 1 month. In the second part of the study, 53 laparoscopies were performed in 15 baboons (6 with a normal pelvis, 9 with endometriosis) during the late follicular and luteal phases of one cycle, with a median time of 3-4 days between each laparoscopy. MAIN OUTCOME MEASURE(S): Peritoneal fluid (PF) was measured and analyzed for white blood cell (WBC) concentrations and, in the second part of the study, for the distribution of lymphocyte subsets (CD3, CD4, CD8, and CD20) and for the presence of cytokines transforming growth factor-beta1, interleukin (IL)-6, and IL-10. RESULT(S): In the first part of the study, PF volumes and WBC concentrations were comparable at the baseline and follow-up laparoscopies. In the second part of the study, PF obtained at the second laparoscopy showed a 10-fold increase in volume, a 3-fold increase in WBC concentration, a 10-fold increase in IL-6 concentration, and a 2-fold increase in transforming growth factor-beta1 concentration when compared with PF obtained at the first laparoscopy. The PF subset of granulocytes and CD3-positive cells was higher and the PF subset of macrophages was lower at follow-up laparoscopies than at the baseline laparoscopy. CONCLUSION(S): Diagnostic laparoscopy can cause peritoneal inflammation in baboons.

The effect of pregnancy on endometriosis in baboons (Papio anubis, Papio cynocephalus).

BACKGROUND: This study was performed to test the hypothesis that endometriosis undergoes regression during pregnancy. METHODS: This study was performed on 11 baboons with histologically proven endometriosis, housed at the Institute of Primate Research, Nairobi, Kenya. In each individual baboon paired laparoscopies were performed prior to and during pregnancy (6 during first and 5 during second trimester of gestation) with an interval of 5 +/- 3 months. During each laparoscopy the number, size and type of endometriosis implants were noted in detail on a pelvic map; the endometriosis score and stage were calculated according to the revised American Fertility Society (AFS) classification. In each baboon the observations prior to and during pregnancy were compared and analysed by Wilcoxon signed rank test (two-tailed). RESULTS: No significant change was observed in the AFS score or stage of endometriosis, or in the number, size and type of endometriotic lesions in baboons during gestation when compared to the nonpregnant state. CONCLUSION: In baboons pregnancy had no significant effect on endometriosis during the first or second trimester of gestation.

The cycle pregnancy rate is normal in baboons with stage I endometriosis but decreased in primates with stage II and stage III-IV disease.

OBJECTIVES: To test the hypothesis that fertility is reduced in baboons with endometriosis. DESIGN: Prospective controlled follow-up study. SETTING: Institute of Primate Research, Nairobi Kenya. SUBJECTS: Seventy-one baboons, including 34 controls (normal pelvis) and 37 animals with histologically proven endometriosis (16 spontaneous and 21 induced). Baboons with endometriosis had minimal (n = 9), mild (n = 14), moderate (n = 7), or severe (n = 7) disease. INTERVENTIONS: Seventy-one baboons were mated during 286 cycles. MAIN OUTCOME MEASURES: Cycle fecundity rate, cycle pregnancy rate, cycle abortion rate. RESULTS: Cycle pregnancy rate (excluding spontaneous abortions) was 15% (44/286) and was comparable between controls (19%, 20/104) and baboons with endometriosis (13%, 24/182). The cycle pregnancy rates were 24%, 10%, 7.5%, and 12.5% in animals with minimal, mild, moderate, and severe endometriosis, respectively. The cycle pregnancy rate was significantly lower in baboons with stage III-IV endometriosis (9%, 6/64) and with stage II disease (10%, 7/73) than in animals with stage I endometriosis (24%, 11/45) or in controls with a normal pelvis (19%). CONCLUSION: The normal cycle pregnancy rate in baboons with stage I endometriosis and the decreased cycle pregnancy rate in baboons with stage II and stage III-IV disease suggest that fertility decreases with the stage of endometriosis in baboons.

Increased prevalence and recurrence of retrograde menstruation in baboons with spontaneous endometriosis.

This study was done to test the hypothesis that the incidence and recurrence of retrograde menstruation is higher in baboons with spontaneous endometriosis than in those without. A total of 399 laparoscopies was performed on 113 female baboons. Group 1 consisted of 84 animals with a normal pelvis (including 23 that later underwent induction of endometriosis and were assigned to group 4), group 2 comprised nine baboons with spontaneous endometriosis acquired during the last 2 years of the study, group 3 had 18 baboons with long-term spontaneous disease, and group 4 comprised 25 animals with induced endometriosis. Retrograde menstruation was defined by the presence of blood-stained peritoneal fluid (red or dark brown) during menses. Recurrence of retrograde menstruation was analysed during the first two laparoscopies in 13 baboons. Peritoneal fluid was 10 times more frequently blood-stained during menses (62%) than during non-menstrual phases (6%). Retrograde menstruation was observed more frequently in animals with spontaneous disease (groups 2 and 3, 83%) than in animals with a normal pelvis (group 1, 51%). Recurrence of retrograde menstruation was observed more frequently in baboons with spontaneous endometriosis (5/5) than in those without (3/8). The results of this study demonstrate that retrograde menstruation is common in baboons, with a higher prevalence and recurrence in animals with spontaneous endometriosis than in those without.

Development of spontaneous endometriosis in baboons.

OBJECTIVE: To determine the incidence of spontaneous endometriosis over a 32-month period in baboons with initially normal pelves. METHODS: In this observational longitudinal study, which was performed at the Institute of Primate Research, Nairobi (Kenya), 24 baboons with laparoscopically confirmed normal pelves underwent 67 serial laparoscopies (mean 2.8 +/- 1.9, median 3, range 1-6) after 1-3 months (n = 8), 4-6 months (n = 11), 7-9 months (n = 9), 10-12 months (n = 17), 13-15 months (n = 6), 16-18 months (n = 4), 19-21 months (n = 3), 22-24 months (n = 4), 25-27 months (n = 1), and 30-32 months (n = 4). During each laparoscopy, the pelvis was examined for the presence of endometriosis. The number, size, and type of endometriotic implants were noted on a pelvic map, and the endometriosis score and stage were tabulated according to the revised classification of the American Fertility Society. Taking into account the variable length of follow-up, we used life-table analysis to calculate the cumulative incidence of endometriosis. RESULTS: The cumulative incidence of minimal endometriosis (proven by histology) was 64% up to 32 months of follow-up. The eight baboons that developed proven endometriosis were followed over longer periods of time and had undergone more laparoscopies than the animals that did not develop the condition. CONCLUSION: There is a high incidence of minimal endometriosis in baboons, which increases with the time of follow-up and the number of repeat laparoscopies.

Disappearance of the ovulation stigma in baboons (Papio anubis, Papio cynocephalus) as determined by serial laparoscopies during the luteal phase.

OBJECTIVE: To investigate how long an ovulation stigma remains visible as determined by serial laparoscopies performed during the luteal phase in baboons. SUBJECTS AND SETTING: Sixteen female baboons with a normal pelvis (n = 6) and with endometriosis (n = 10) housed at the Institute of Primate Research, Nairobi, Kenya. INTERVENTIONS: Fifty-six laparoscopies were carried out before ovulation (n = 7) and serially during the luteal phase (n = 49; 3 +/- 1 per baboon): 1 to 2 days (n = 2), 4 to 5 days (n = 15), 8 to 9 days (n = 11), 12 to 13 days (n = 12), and 16 to 17 days (n = 9) after ovulation. MAIN OUTCOME MEASURE: During each laparoscopy the ovaries were screened systematically for the presence and size of an ovulation stigma and/or corpus luteum (CL). RESULTS: When the laparoscopy was done within 5 days after ovulation, a fresh ovulation stigma was observed in all nine baboons with a normal pelvis or minimal endometriosis, but only in four of seven animals with mild to severe disease. If a fresh ovulation stigma had been observed within 5 days after ovulation (n = 13), it gradually became smaller but remained visible 8 to 9 days after ovulation in 91%, at 12 to 13 days after ovulation in 75%, and at 16 to 17 days after ovulation in 50% of the primates. CONCLUSION: If a fresh ovulation stigma was observed in baboons within 5 days after ovulation, it diminished in size but remained visible up to 8, 12, and 16 days after ovulation in 91%, 75%, and 50% of animals, respectively. Therefore, diagnostic laparoscopies for the detection of an ovulation stigma in baboons should be performed in the early luteal phase.

Increased incidence and recurrence of recent corpus luteum without ovulation stigma (luteinized unruptured follicle syndrome?) in baboons with endometriosis.

OBJECTIVE: To test the hypothesis that a recent corpus luteum (CL) without fresh ovulation stigma (OS) can be found with a higher incidence and recurrence in baboons with endometriosis and is associated with a reduced egg recovery rate after uterine flush. METHODS: One hundred thirty-eight laparoscopies were performed in the early luteal phase of 52 cycles in 32 female baboons with a normal pelvis (controls) and of 86 cycles in 21 animals with endometriosis. The incidence and recurrence of a recent CL without OS was studied during each laparoscopy and during the first three laparoscopies in 15 baboons (five controls, ten with endometriosis), respectively. The association between the presence of a recent CL without OS and the egg recovery rate was evaluated during 65 cycles in 21 baboons after uterine flush. RESULTS: When all 138 laparoscopies were analyzed, the incidence of a recent CL without OS was higher (P < .03) in animals with stage II-IV endometriosis (35%) than in those with stage I disease (19%) or controls (11%). Both the incidence (seven of ten) and recurrence (three of ten) of a recent CL without OS were higher in baboons with endometriosis than in controls (zero of five, P < .02) when studied during the first three laparoscopies. Laparoscopies in primates having a recent CL without OS were associated with a lower egg recovery rate (13%) than in animals with recent CL and OS (54%, P = .005). CONCLUSION: A recent CL without OS was associated with a reduced egg recovery rate and could be found with a higher incidence and recurrence in baboons with endometriosis than in controls, suggesting that luteinized unruptured follicle syndrome exists and could contribute to endometriosis-associated subfertility.

Serial laparoscopies over 30 months show that endometriosis in captive baboons (Papio anubis, Papio cynocephalus) is a progressive disease.

OBJECTIVE: To test the hypothesis that spontaneous endometriosis is a progressive disease in baboons. DESIGN AND SETTING: Prospective cohort study, Institute of Primate Research, Nairobi, Kenya. PARTICIPANTS: Twelve baboons with histologically proven spontaneous endometriosis. INTERVENTIONS: Fifty-four serial laparoscopies (4.2 +/- 1.9 per animal, range 1 to 7) were performed after 1 to 3 months (n = 2), 4 to 6 months (n = 1), 7 to 9 months (n = 6), 10 to 12 months (n = 17), 13 to 15 months (n = 7), 16 to 18 months (n = 1), 19 to 21 months (n = 8), 22 to 24 months (n = 8), 25 to 27 months (n = 2), and 30 to 32 months (n = 2). MAIN OUTCOME MEASURE: During each laparoscopy the pelvis was examined for the presence of endometriosis. The number, size, and type of endometriotic implants were noted on a pelvic map and both endometriosis score and stage were calculated. Remodeling was defined as a change in laparoscopic appearance (typical, subtle, suspicious) of an individual endometriotic lesion. Data were analyzed by a signed rank test. RESULTS: Endometriosis was progressive as shown by the significant increase in the number and surface of lesions and in endometriosis scores after 24 months. The total number of endometriotic lesions after 24 months consisted of 69% new (and mostly subtle) implants, 10% remodeled lesions, and 21% unchanged implants. CONCLUSIONS: This study demonstrated that endometriosis in captive baboons undergoing repeated laparoscopies is a dynamic and moderately progressive disease with periods of development and regression and active remodeling between different types of lesions.

The effects of immunosuppression on development and progression of endometriosis in baboons (Papio anubis).

OBJECTIVE: To test the hypothesis that immunosuppression increases the development and progression of endometriosis in baboons. DESIGN: Experimental controlled study. SETTING: Institute of Primate Research, Nairobi, Kenya. PARTICIPANTS: Thirty-two baboons (8 with normal pelvis, 10 with spontaneous endometriosis, and 14 with endometriosis induced by intraperitoneal seeding of menstrual endometrium). INTERVENTION: Daily injection of 0.8 mg/kg IM methylprednisolone and 2 mg/kg azathioprine for 3 months in 16 baboons (4 with normal pelvis, 5 with spontaneous endometriosis, and 7 with induced endometriosis). No treatment was given to the remaining 16 primates. MAIN OUTCOME MEASURES: The change in number and surface area (mm2) of endometriotic lesions was evaluated by laparoscopy in all baboons after 3 months, in 8 animals with induced endometriosis and in 9 primates with spontaneous disease after 7 and 12 months, respectively. RESULTS: Immunosuppressed baboons with spontaneous endometriosis had a significantly higher number and larger surface area of endometriotic lesions than nontreated animals. However, immunosuppressed and nontreated primates with induced endometriosis were comparable with respect to both number and surface area of implants. A transient decrease in typical lesions was noted during immunosuppression. Immunosuppression did not cause the development of endometriosis in baboons with previously documented normal pelvis. CONCLUSION: Immunosuppression may increase the progression of endometriosis in baboons with spontaneous disease.

Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis).

OBJECTIVE: The Sampson hypothesis of retrograde menstruation as a cause of endometriosis was tested by determining the effect of intrapelvic injection of menstrual versus luteal endometrium on the incidence, peritoneal involvement, and stage of endometriosis. STUDY DESIGN: Seventeen baboons were injected retroperitoneally with luteal (n = 6) or menstrual (n = 7) endometrium and intraperitoneally with menstrual endometrium (n = 4). Laparoscopies were performed after 2 months in all animals and after 5 and 12 months in six and five primates injected with luteal and menstrual endometrium, respectively. RESULTS: The peritoneal endometriosis surface area, number of implants, and incidence of typical and red subtle lesions were significantly higher after retroperitoneal injection of menstrual than of luteal endometrium. By use of menstrual endometrium intraperitoneal seeding was more successful in causing endometriosis than was retroperitoneal injection. No significant changes in number or surface area of endometriotic lesions induced with retroperitoneal injection of luteal endometrium after 5 months were observed in the six baboons. At repeat laparoscopy 12 months after intrapelvic injection of menstrual endometrium progression was recorded in three of four regularly cycling animals, whereas regression was evident in one baboon that had become amenorrheic after induction. CONCLUSION: Intrapelvic injection of menstrual endometrium can cause peritoneal endometriosis and offers experimental evidence supporting the Sampson hypothesis.

High intraabdominal pressure: effects on clinical parameters and lung pathology in baboons (Papio cynocephalus and Papio anubis).

OBJECTIVE: The risks of a high intraabdominal pressure during laparoscopy are poorly documented. These aspects were studied in a relevant nonhuman primate model, the baboon (Papio anubis, Papio cynocephalus). STUDY DESIGN: The animals used were to be killed at the completion of a vaccine project. They were anesthetized and intubated but allowed to breathe spontaneously. In group 1 (n = 10) a fixed intraabdominal pressure (between 10 and 35 cm H2O [7 and 26 mm Hg]) was applied over 30 minutes. In group 2 (n = 7) the intraabdominal pressure was increased up to a maximum of 105 cm H2O (77 mm Hg). Blood vessels of the parietal peritoneum and omentum were systematically opened from 30 cm H2O (22 mm Hg) onward. Respiration and pulse rate were measured regularly, and the degree of respiratory distress was assessed. After death of the baboons a necropsy was carried out immediately to study the degree of lung atelectasis. RESULTS: In group 1 the respiration rate increased and the heart rate decreased. At an intraabdominal pressure of > or = 30 cm H2O (22 mm Hg) moderate respiratory distress was seen after 20 minutes. In group 2 one animal had a bilateral pneumothorax at a pressure of 60 cm H2O (44 mm Hg) and died at 90 cm H2O (66 mm Hg). Severe respiratory distress was observed in the other six animals. Severe lung atelectasis was present in only one of the five primates with moderate respiratory distress of group 1 and in all baboons of group 2. CONCLUSION: An increase of intraabdominal pressure up to 105 cm H2O (77 mm Hg) combined with intraabdominal blood vessel injury is not lethal in most baboons.