Jeffrey M. Goldberg

Pathogenic mechanisms in endometriosis-associated infertility

OBJECTIVE To review the mechanisms by which endometriosis may affect reproductive function. DESIGN Review of the English literature from 1986 to 2007 after searching Medline, EMBASE, Cochrane, and BIOSIS, as well as relevant meeting abstracts. SETTING Fertility research center and obstetrics and gynecology department in a tertiary care hospital. RESULT(S) There is compelling evidence in the literature that endometriosis has detrimental effects on ovarian and tubal function and uterine receptivity, resulting in female infertility. The mechanisms of infertility associated with endometriosis remain controversial and include abnormal folliculogenesis, elevated oxidative stress, altered immune function, and hormonal milieu in the follicular and peritoneal environments, and reduced endometrial receptivity. These factors lead to poor oocyte quality, impaired fertilization, and implantation. CONCLUSION(S) Through unraveling the mechanisms by which endometriosis leads to infertility, researchers are sure to find a nonsurgical means to diagnose endometriosis, most likely through serum and peritoneal markers. Cytokines, interleukins, oxidative stress markers, and soluble cellular adhesion molecules all show potential to be used as a reliable marker for diagnosing endometriosis. After analyzing the pathogenic mechanisms of endometriosis, it seems that the future treatment of this entity may include cyclo-oxygenase-2 inhibitors, immunomodulators, or hormonal suppressive therapy to eliminate the need for surgical treatment of endometriosis.

Robotic-assisted laparoscopic microsurgical tubal anastomosis: a human pilot study☆

OBJECTIVE To evaluate the feasibility and safety of a robotic device to perform a laparoscopic tubal anastomosis. DESIGN Prospective pilot study. SETTING Tertiary care medical center. PATIENT(S) Ten patients with previous tubal ligations underwent laparoscopic tubal ligation reversal using a robotic suturing device. INTERVENTION(S) Tubal surgery was performed with a robotic system. A two-layered closure was used for all tubes. Four stitches of 8-0 polygalactin sutures were used for each layer. MAIN OUTCOME MEASURE(S) Tubal patency; secondary measures were pregnancy rates, complications, and operative time. RESULT(S) The procedure was completed successfully in all 10 patients. No patient required conversion to an open procedure. The mean time (+/-SD) required to complete the anastomosis of both tubes was 159 +/- 33.8 minutes. Chromotubation at the end of the procedure showed patency in all tubes anastomosed. A postoperative hysterosalpingogram 6 weeks after surgery demonstrated patency in 17 of the 19 (89%) tubes anastomosed. There have been five pregnancies so far. There were no complications. CONCLUSION(S) Robotic technology can be used safely to create laparoscopic microsurgical anastomoses with adequate patency rates. Robotic technology has the potential to make laparoscopic microsuturing easier.

Vitamin C and vitamin E supplementation reduce oxidative stress–induced embryo toxicity and improve the blastocyst development rate

To evaluate the adverse effects of exogenously induced reactive oxygen species (ROS) on mouse embryo development by using the 12-phorbol 13-myristate acetate (PMA)-activated leukocyte model as a source of ROS, and to examine the protective effect of antioxidant supplementation (vitamin C and vitamin E). Prospective study. Research laboratory. Effects of ROS on the blastocyst development rate in the presence and absence of antioxidant supplementation. After incubation with the PMA-activated leukocyte supernatant, the median (25th, 75th percentile) rate of blastocyst development significantly decreased from 73% (60%, 80%) after 3 hours to 30% (20%, 40%) after 6 hours compared with control reactions (86% [80%, 100%]). Co-incubating the embryos with vitamin C (50 microM) and the PMA-activated supernatant significantly increased the blastocyst development rate from 73% (60%, 80%) to 90% (80%, 91%) at 3 hours and from 30% (20%, 40%) to 91% (89%, 91%) at 6 hours-a level similar to that of control reactions. The blastocyst development rate increased after vitamin E supplementation (400 microM) at 6 hours, but not significantly and not by as much as after vitamin C supplementation. Exposure of mouse embryos to ROS for extended periods results in embryotoxicity. Vitamin C is more effective than vitamin E in reversing ROS-induced mouse embryo toxicity.

Effect of diethylstilbestrol on reproductive function

OBJECTIVE To review the effects of in utero exposure to diethylstilbestrol (DES) on müllerian development and subsequent reproductive function. DESIGN The literature on DES and reproductive function was reviewed and summary data are presented. The studies were identified through the computerized MEDLINE database and a manual search of relevant bibliographies. RESULT(S) In utero exposure to DES resulted in reduced fertility and increased rates of ectopic pregnancy, spontaneous abortion, and preterm delivery. CONCLUSION(S) An understanding of the reproductive performance of women who were exposed to DES in utero is useful for counseling these patients regarding their risks and treatment options.

Tubal anastomosis by robotic compared with outpatient minilaparotomy

OBJECTIVE: To compare tubal anastomosis by robotic system compared with outpatient minilaparotomy. METHODS: In this retrospective case–control study, women were identified by current procedural terminology code for tubal anastomosis. We included all cases of tubal anastomosis for reversal of a prior tubal ligation by either outpatient minilaparotomy or robotic system technique. Cases performed by laparoscopy without aid of the robot were excluded. Comparisons were based on Fishers exact, &khgr;2, and Wilcoxon rank sum tests. RESULTS: There were 26 cases of tubal anastomosis performed with the robot and 41 cases performed by outpatient minilaparotomy. The two groups were comparable in age, body mass index, and parity. Anesthesia time for the robotic technique (median with interquartile range) was 283 (267–290) minutes compared with 205 (170–230) minutes with outpatient minilaparotomy (P<.001). Surgical times for the robot and minilaparotomy were 229 (205–252) minutes and 181 (154–202) minutes respectively (P=.001). Hospitalization times, pregnancy, and ectopic pregnancy rates were not significantly different. The robotic technique was more costly. The median difference in costs of the procedures was

Importance of reactive oxygen species in the peritoneal fluid of women with endometriosis or idiopathic infertility

1,446 (95% confidence interval

Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles

1,112–1,812) (P<.001). The time to return to work was significantly shorter in the robotic system group by approximately 1 week (P=.013). CONCLUSION: Robotic surgery for tubal anastomosis was successfully accomplished without conversion to laparotomy. The robotic technique for tubal anastomosis required significantly prolonged surgical and anesthesia times over outpatient minilaparotomy (P≤.001). Costs were higher with the robotic technique. Return to normal activity was shorter with the robotic technique. LEVEL OF EVIDENCE: II

Robotically assisted laparoscopic microsurgical uterine horn anastomosis

OBJECTIVE To determine whether reactive oxygen species in peritoneal fluid might be a factor in infertility. DESIGN Prospective study. SETTING Andrology laboratory and gynecology clinic at a tertiary care facility. PATIENT(S) Women with endometriosis (n = 15) or idiopathic infertility (n = 11) who underwent laparoscopy for infertility. Patients undergoing tubal ligation served as controls (n = 13). INTERVENTION(S) Aspiration of peritoneal fluid. MAIN OUTCOME MEASURE(S) Reactive oxygen species levels, presence of polymorphonuclear granulocytes, and leukocyte distribution in peritoneal fluid. RESULT(S) Reactive oxygen species were present in the peritoneal fluid of patients with endometriosis, idiopathic infertility, and tubal ligation. Levels of reactive oxygen species did not show a statistically significant difference between patients with endometriosis and the control group in either unprocessed or processed (cell-free) peritoneal fluid, but did differ significantly between patients with idiopathic infertility and controls in processed peritoneal fluid. Polymorphonuclear granulocytes (> 1 x 10(6)/mL) were not present in the peritoneal fluid of any patient. Macrophage concentrations of peritoneal fluid did not differ significantly between controls and patients with endometriosis or idiopathic infertility. CONCLUSION(S) Reactive oxygen species in the peritoneal fluid may not affect fertility directly in women with endometriosis; however, they may have a role in patients with idiopathic infertility.

The association between heavy metals, endometriosis and uterine myomas among premenopausal women: National Health and Nutrition Examination Survey 1999–2002

BackgroundTime-lapse imaging combined with embryo morphokinetics may offer a non-invasive means for improving embryo selection. Data from clinics worldwide are necessary to compare and ultimately develop embryo classifications models using kinetic data. The primary objective of this study was to determine if there were kinetic differences between embryos with limited potential and those more often associated with in vitro blastocyst formation and/or implantation. We also wanted to compare putative kinetic markers for embryo selection as proposed by other laboratories to what we were observing in our own laboratory setting.MethodsKinetic data and cycle outcomes were retrospectively analyzed in patients age 39 and younger with 7 or more zygotes cultured in the Embryoscope. Timing of specific events from the point of insemination were determined using time-lapse (TL) imaging. The following kinetic markers were assessed: time to syngamy (tPNf), t2, time to two cells (c), 3c (t3), 4c ( t4), 5c (t5), 8c (t8), morula (tMor), start of blastulation (tSB); tBL, blastocyst (tBL); expanded blastocyst (tEBL). Durations of the second (cc2) and third (cc3) cell cycles, the t5-t2 interval as well as time to complete synchronous divisions s1, s2 and s3 were calculated. Incidence and impact on development of nuclear and cleavage anomalies were also assessed.ResultsA total of 648 embryos transferred on day 5 were analyzed. The clinical pregnancy and implantation rate were 72% and 50%, respectively. Morphokinetic data showed that tPNf, t2,t4, t8, s1, s2,s3 and cc2 were significantly different in embryos forming blastocysts (ET or frozen) versus those with limited potential either failing to blastulate or else forming poor quality blastocysts ,ultimately discarded. Comparison of embryo kinetics in cycles with all embryos implanting (KID+) versus no implantation (KID-) suggested that markers of embryo competence to implant may be different from ability to form a blastocyst. The incidence of multinucleation and reverse cleavage amongst the embryos observed was 25% and 7%, respectively. Over 40% of embryos exhibiting these characteristics did however form blastocysts meeting our criteria for freezing.ConclusionsThese data provide us with a platform with which to potentially enhance embryo selection for transfer.

Present and future fertility preservation strategies for female cancer patients.

OBJECTIVE To evaluate the feasibility, safety, and sterility issues with regard to the use of a robotic device to perform uterine horn anastomosis in a live porcine model. DESIGN Prospective animal study. SETTING Landrace-Yorkshire pigs in a conventional laboratory setting. INTERVENTION(S) Six female pigs underwent laparoscopic bipolar electrocoagulation of the distal uterine horns. Two weeks later, the uterine horns were reanastomosed laparoscopically with use of a robotic system for microsuturing. Necropsy was performed 4 weeks later to assess postoperative adhesions and anastomosis patency. MAIN OUTCOME MEASURE(S) Tubal patency; secondary measures were operative time, complications, and surgeon fatigue. RESULT(S) The mean (+/-SD) total operative time per animal was 170+/-34 minutes including setting up and dismantling the robotic arms. The robot functioned well with only minor technical problems. All pigs survived both surgeries with no perioperative complications related to the use of the robot. Patency was confirmed after completing each anastomosis (12 anastomoses; 100% patency). Four weeks later, necropsy showed that eight anastomoses were still patent (67%). Only one pig had bilateral occlusion. Surgeons fatigue was mild for each animal study. CONCLUSION(S) Robotic technology can be used safely in creating laparoscopic microsurgical anastomoses. The robot functioned properly in a sterile operating room environment. Adequate patency rates were achieved during the acute phase and at 4-week follow-up. Robotic technology has the potential to make laparoscopic microsuturing easier.