Luteal granulosa cells from natural cycles are more capable of maintaining their viability, steroidogenic activity and LH receptor expression than those of stimulated IVF cycles.

STUDY QUESTION: Are there any differences in the molecular characteristics of the luteal granulosa cells (GC) obtained from stimulated versus non-stimulated (natural) IVF cycles that may help explain the defective luteal phase in the former? SUMMARY ANSWER: Luteal GC of stimulated IVF cycles, particularly those of agonist-triggered antagonist cycles, are less viable ex vivo, express LH receptor and anti-apoptotic genes at lower levels, undergo apoptosis earlier and fail to maintain their estradiol (E2) and progesterone (P4) production in comparison to natural cycle GC. WHAT IS KNOWN ALREADY: Luteal function is defective in stimulated IVF cycles, which necessitates P4 and/or hCG administration (known as luteal phase support) in order to improve clinical pregnancy rates and prevent miscarriage. The luteal phase becomes shorter and menstruation begins earlier than a natural cycle if a pregnancy cannot be achieved, indicative of early demise of corpus luteum (premature luteolysis). Supra-physiological levels of steroids produced by multiple corpora luteae in the stimulated IVF cycles are believed to inhibit LH release directly via negative feedback actions on the hypothalamic-pituitary-ovarian axis resulting in low circulating levels of LH and a defective luteal phase. We hypothesized that some defects in the viability and steroidogenic activity of the luteal GC of the stimulated IVF cycles might contribute to this defective luteal phase in comparison to natural cycle GC. This issue has not been studied in human before. STUDY DESIGN, SIZE, DURATION: A comparative translational research study of ex vivo and in vitro models of luteal GC recovered from IVF patients undergoing natural versus stimulated IVF cycles was carried out. Luteinized GC were obtained from 154 IVF patients undergoing either natural (n = 22) or stimulated IVF cycles with recombinant FSH and GnRH agonist (long) (n = 44), or antagonist protocol triggered conventionally either with recombinant hCG (n = 46) or with a GnRH agonist (n = 42). GC were maintained in vitro for up to 6 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cellular viability (YO-PRO-1 staining), the expression of the steroidogenic enzymes, pro-apoptotic genes [Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX) and Caspase-3 (CASP3)], anti-apoptotic genes [RAC-alpha serine/threonine-protein kinase (AKT-1) and Bcl-2-like protein 2 (BCL2-L2)], LH receptor, vascular endothelial growth factor (VEGF) (using real-time quantitative PCR at mRNA level and western blot immunoprecipitation assay at protein level) and in vitro E2 and P4 production (electrochemiluminescence immunoassay) were compared in GC among the groups. MAIN RESULTS AND THE ROLE OF CHANCE: Natural cycle GC were significantly more viable ex vivo (88%) compared to their counterparts of the stimulated IVF cycles (66, 64 and 37% for agonist and antagonist cycles triggered with hCG and GnRH agonist respectively, P < 0.01). They were also more capable of maintaining their vitality in culture compared to their counterparts from the stimulated IVF cycles: at the end of the 6-day culture period, 74% of the cells were still viable whereas only 48, 43 and 22% of the cells from the agonist and antagonist cycles triggered with hCG and agonist respectively, were viable (P < 0.01). The mRNA expression of anti-apoptotic genes (AKT-1 and BCL2-L2) was significantly lower, while that of pro-apoptotic genes (BAD, BAX and CASP3) was significantly higher in the stimulated cycles, particularly in the agonist-triggered antagonist cycles, compared to natural cycle GC (P < 0.01 for long protocol and antagonist hCG trigger, P < 0.001 for agonist trigger). The expression of steroidogenic enzymes (stAR, SCC, 3ß-HSD and aromatase) and VEGF was significantly higher in the agonist and hCG-triggered antagonist cycles compared to natural cycle GC. Therefore, in vitro E2 and P4 production in cells from the stimulated IVF cycles was significantly higher than their counterparts obtained from the natural cycles in the first 2 days of culture. However, after Day 2, their viability and hormone production began to decline very rapidly with the most drastic decrease being observed in the agonist-triggered cycles. By contrast, natural cycle GC maintained their viability and produced E2 and P4 in increasing amounts in culture up to 6 days. In vitro P production and the mRNA and protein expression of LH receptor, VEGF and 3ß-HSD were most defective in the agonist-triggered antagonist cycles compared to natural and agonist and hCG-triggered antagonist cycles. In vitro hCG treatment of a subset of the cells from the agonist-triggered cycles improved their viability, increased E2 and P4 production in vitro and up-regulated the mRNA expression of anti-apoptotic gene BCL-L2 together with steroidogenic enzymes stAR, SCC, 3B-HSD, LH receptor and VEGF. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The limitations include analysis of luteinized GC only might not reflect the in vivo mechanisms involved in survival and function of the whole corpus luteum; GC recovered during oocyte retrieval belong to a very early stage of the luteal phase and might not be representative; effects of ovulation triggered with hCG may not equate to the endogenous LH trigger; the clinical characteristics of the patients may vary among the different groups and it was not possible to correlate stimulation-related molecular alterations in luteal GC with the clinical outcome, as no oocytes have been utilized yet. Therefore, our findings do not conclusively rule out the possibility that some other mechanisms in vivo may also account for defective luteal function observed in stimulated IVF cycles. WIDER IMPLICATIONS OF THE FINDINGS: Ovarian stimulation is associated with significant alterations in the viability and steroidogenic activity of luteal GC depending on the stimulation protocol and mode of ovulation trigger. Reduced survival and down-regulated expression of 3B-HSD, LH receptor and VEGF leading to compromised steroid production in stimulated cycles, and particularly in the agonist-triggered cycles, may at least in part help explain why the luteal phase is defective and requires exogenous support in these cycles. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest.

Combined modalities for the prevention of ovarian hyperstimulation syndrome following an excessive response to stimulation.

Although the classification and management of ovarian hyperstimulation syndrome (OHSS) are well described in the literature, little attention has been given to modalities that aim to prevent its occurrence. In this retrospective study, we sought to investigate whether a combination of modalities in addition to GnRH agonist triggering in GnRH antagonist cycles could result in better prevention of OHSS. The study included 170 hyperresponder patients who were stimulated with GnRH antagonist protocol and were triggered with GnRH agonist for final oocyte maturation. Freeze all embryos was performed in all patients. The intervention group included treatment with dopamine agonist and restarting the GnRH antagonist. Of the 170 patients included, 63 were included in the intervention group. Compared to no intervention, women in the intervention group were more likely to have: menses within 7 days of the oocyte retrieval, smaller ovarian diameter, the absence of free pelvic fluid, less hemoconcentration and higher serum sodium levels. It can be concluded that combining other modalities in addition to triggering with GnRH agonist in GnRH antagonist cycles, results in targeting several pathways that lead to OHSS and result in rapid resolution of signs of ovarian hyperstimulation.

Do endometriomas grow during ovarian stimulation for assisted reproduction? A three-dimensional volume analysis before and after ovarian stimulation.

Whether endometriomas grow because of supraphysiological oestradiol levels attained during ovarian stimulation for assisted reproduction techniques is a concern. In this prospective study, 25 women with 28 endometriomas underwent three-dimensional ultrasound using sono-automated volume calculation software. Endometrioma volume was measured on the first day of gonadotrophin injection (V1) and the day of ovulation trigger (V2). Nine (36%) women were stimulated in a gonadotrophin releasing hormone antagonist protocol (GnRH), 13 (52%) in a long, and three (12%) in an ultra-long GnRH agonist protocol. Mean duration of stimulation was 10.3 days with median total gonadotrophin dose of 4500 IU/day. Median number of cumulus oocyte complexes was five, and metaphase-two oocytes was four. None of the endometriomas were punctured during oocyte retrieval. Median V1 was 22.2 ml (12-30 ml) and median V2 was 24.99 ml (11.2-37.4 ml) with P = 0.001. Twenty-three out of 28 endometriomas (82%) grew to some extent during ovarian stimulation. Endometrioma growth was positively correlated with prestimulation cyst volume (Correlation coefficient 0.664; P < 0.01). Although the 3-ml average growth was statistically significant, it could be regarded as clinically insignificant.

Which is worse? Comparison of ART outcome between women with primary or recurrent endometriomas.

STUDY QUESTION: Are live birth rates (LBR) different after ART cycles between women with primary or recurrent endometrioma? SUMMARY ANSWER: Women with recurrent endometrioma have similar LBR as compared to patients with primary endometrioma. WHAT IS ALREADY KNOWN: Recurrence rate can be as high as 29% after endometrioma excision. Prior studies on management of endometrioma before ART involve primary endometriomas. There is limited information regarding the prognosis of women with recurrent endometriomas. STUDY DESIGN, SIZE, DURATION: A multicenter retrospective cohort study, including 76 women with primary and 82 women with recurrent endometriomas treated at the participating centers over a 6-year period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma who underwent ART at three academic ART centers. Couples with another indication for ART were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Female age, median number of prior failed ART cycles, proportion of patients with bilateral endometrioma (28 versus 28.9%), ovarian stimulation protocols, and total gonadotropin consumption were similar between the study groups. Numbers of metaphase two oocytes (5 versus 6), number of embryos transferred, and the proportion of patients undergoing blastocyst transfer were similar across the study groups. Clinical pregnancy rates (36.6 versus 34.2%, absolute difference 2.4%, 95% CI: -12.5 to 17.3%, P = 0.83) and LBR (35.4 versus 30.3%, absolute difference 5.1%, 95% CI: -9.5 to 19.7%, P = 0.51) per started cycle in recurrent and primary endometrioma were similar. Comparable success rates were also confirmed with logistic regression analysis (OR: 1.14, 95% CI: 0.78-0.57, P = 2.3). LIMITATIONS, REASONS FOR CAUTION: The retrospective design has inherent limitations. Some women with severely decreased ovarian reserve after primary endometrioma excision may not have pursued further treatment. WIDER IMPLICATIONS OF THE FINDINGS: The management of endometrioma prior to ART is controversial but a different management strategy is not required for recurrent endometriomas. Since recurrent endometriomas do not have a worse impact on ART outcome than primary endometriomas, and repeat surgery has a higher risk for complications, conservative management without surgery can be justified. STUDY FUNDING/COMPETING INTEREST(S): No funding or competing interests to declare. TRIAL REGISTRATION NUMBER: None.

Short and long term outcomes of children conceived with assisted reproductive technology.

Despite their wide and global use, possible short and long-term effects of fertility treatments on children is not well-established. In this review, birth defects and perinatal complications and their relationship with assisted reproductive technology (ART), along with long-term effects of ART on cardiovascular system, metabolism, behavior, cognitive skills, and childhood cancers are discussed. Children conceived through ART are at increased risk for birth defects and perinatal complications such as preterm delivery, low birth weight and small for gestational age. Parental characteristics, underlying infertility etiology and ART procedures themselves may contribute to this. The long-term effects of ART are difficult to establish. Studies so far report that ART children have normal social, emotional, cognitive, and motor functions. Likewise, despite some minor inconsistencies in some studies, they do not seem to be at increased risk for childhood cancers. However, there are a number of studies that imply vascular system may be adversely affected by ART and its possible consequences should be further investigated with follow up studies. Large scale studies with long-term follow up periods are required to determine the effects of ART on conceived children.

Does the use of gonadotropin-releasing hormone antagonists in natural IVF cycles for poor responder patients cause more harm than benefit?

Poor ovarian response to controlled ovarian stimulation (COS) is one of the most critical factors that substantially limits the success of assisted reproduction techniques (ARTs). Natural and modified natural cycle IVF are two options that could be considered as a last resort. Blocking gonadotropin-releasing hormone (GnRH) actions in the endometrium via GnRH receptor antagonism may have a negative impact on endometrial receptivity. We analysed IVF outcomes in 142 natural (n = 30) or modified natural (n = 112) IVF cycles performed in 82 women retrospectively. A significantly lower proportion of natural cycles reached follicular aspiration compared to modified natural cycles (56.7% vs. 85.7%, p < 0.001). However, the difference between the numbers of IVF cycles ending in embryo transfer (26.7% vs. 44.6%) was not statistically significant between natural cycle and modified natural IVF cycles. Clinical pregnancy (6.7% vs. 7.1%) and live birth rates per initiated cycle (6.7% vs. 5.4%) were similar between the two groups. Notably, the implantation rate was slightly lower in modified natural cycles (16% vs. 25%, p > 0.05). There was a trend towards higher clinical pregnancy (25% vs. 16%) and live birth (25% vs. 12%) rates per embryo transfer in natural cycles compared to modified natural cycles, but the differences did not reach statistical significance.

The Impact of Endometriosis and Its Treatment on Ovarian Reserve.

Endometriosis is a chronic disease mostly affecting women at reproductive age. There is a clear association between endometriosis and infertility; however, exact mechanisms are unknown. Some evidence suggests an adverse effect on oocytes. Endometriosis and its surgical treatment can affect quantitative ovarian reserve as well. In the presence of endometriomas, serum level of anti-Müllerian hormone (AMH) seems a more reliable marker of ovarian reserve than antral follicle count. Women with endometrioma have decreased serum AMH levels as compared with healthy controls. This is further declined after surgical excision, and the decline seems permanent. Bipolar cauterization of the ovary seems to be playing a role on ovarian damage. Extraovarian endometriosis and its surgical treatment can also be associated with decreased ovarian reserve, but there is limited information. Patients with endometriosis should be informed about fertility preservation options, especially in the presence of bilateral endometriomas or prior to surgery.

Effect of hemostatic method on ovarian reserve following laparoscopic endometrioma excision; comparison of suture, hemostatic sealant, and bipolar dessication. A systematic review and meta-analysis.

We reviewed the literature to determine whether different hemostatic methods used following laparoscopic endometrioma excision have differing effects on ovarian reserve. We performed a systematic literature search using the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and Ovid MEDLINE In-Process & Other Non-Indexed Citations databases to identify studies comparing the rate of change in levels of serum anti-Müllerian hormone (AMH) at 3 months after laparoscopic endometrioma excision using bipolar dessication (BD) or suturing/application of a hemostatic sealant (HS) for hemostasis. Abstracts of the annual meetings of the American Society of Reproductive Medicine, the European Society of Human Reproduction and Embryology, and the American Association of Gynecological Laparoscopists were searched as well. A total of 712 articles were identified, of which 6 were included in the qualitative analysis. Four studies involving 213 women were included in the meta-analysis. Our qualitative analysis suggested that BD is more detrimental to ovarian reserve than alternative hemostatic methods. There is moderate-quality evidence favoring HS and low-quality evidence favoring sutures over BD. The meta-analysis also showed that alternative hemostatic methods are associated with significantly less decline in ovarian reserve compared with BD. The mean decline in serum AMH levels was 6.95% less with alternative hemostatic methods than with BD (95% CI, -13.0% to -0.9%; p = .02) at 3 months after surgery. According to the best available evidence, the use of BD should be cautiously limited, even avoided when possible, during endometrioma excision in women who desire to have children.

Gonadotropin-releasing hormone agonist triggering of oocyte maturation in assisted reproductive technology cycles.

Gonadotropin-releasing hormone agonists (GnRHa) have gained increasing attention in the last decade as an alternative trigger for oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS). They provide a short luteinizing hormone (LH) peak that limits the production of vascular endothelial growth factor, which is the key mediator leading to increased vascular permeability, the hallmark of OHSS. Initial studies showed similar oocyte yield and embryo quality compared with conventional human chorionic gonadotropin (hCG) triggering; however, lower pregnancy rates and higher miscarriage rates were alarming in GnRHa triggered groups. Therefore, two approaches have been implemented to rescue the luteal phase in fresh transfers. Intensive luteal phase support (iLPS) involves administiration of high doses of progesterone and estrogen and active patient monitoring. iLPS has been shown to provide satisfactory fertilization and clinical pregnancy rates, and to be especially useful in patients with high endogenous LH levels, such as in polycystic ovary syndrome. The other method for luteal phase rescue is low-dose hCG administiration 35 hours after GnRHa trigger. Likewise, this method results in statistically similar ongoing pregnancy rates (although slightly lower than) to those of hCG triggered cycles. GnRHa triggering decreased OHSS rates dramatically, however, none of the rescue methods prevent OHSS totally. Cases were reported even in patients who underwent cryopreservation and did not receive hCG. GnRH triggering induces a follicle stimulating hormone (FSH) surge, similar to natural cycles. Its possible benefits have been investigated and dual triggering, GnRHa trigger accompanied by a simultaneous low-dose hCG injection, has produced promising results that urge further exploration. Last of all, GnRHa triggering is useful in fertility preservation cycles in patients with hormone sensitive tumors. In conclusion, GnRHa triggering accompanied by appropriate luteal phase rescue protocols is a relatively safe option for patients at high risk for OHSS.

Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG.

STUDY QUESTION: Is severe early ovarian hyperstimulation syndrome (OHSS) completely prevented with the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol? SUMMARY ANSWER: Severe early OHSS can occur even after the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol. WHAT IS KNOWN ALREADY: Prior studies including over 200 women who received the GnRH agonist trigger and 1500 hCG luteal rescue protocol have reported complete prevention of severe early OHSS. Only a few late OHSS cases have been reported and it has been suggested that this protocol can be safely applied to any women under risk. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included all women who were at high risk of OHSS and were given the GnRH agonist trigger plus hCG luteal rescue protocol between December 2008 and August 2012 in the two participating centers. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 23 women with a mean estradiol level of 4891 ± 2214 pg/ml and a mean number of >12 mm follicles of 20 ± 6 on the day of ovulation triggering. OHSS was categorized according to the Golan criteria. MAIN RESULTS AND THE ROLE OF CHANCE: Overall 6 of the 23 (26%) women developed severe OHSS. Five women had severe early OHSS requiring ascites drainage and hospitalization and three of these women did not undergo embryo transfer. The number of follicles measuring 10-14 mm on the day of triggering was significantly different between women who developed severe early OHSS and those who did not. LIMITATIONS, REASONS FOR CAUTION: The small number of women with severe early OHSS may have prevented identification of other significant risk factors. WIDER IMPLICATIONS OF THE FINDINGS: Although the GnRH agonist plus 1500 IU hCG luteal rescue protocol significantly decreases the risk of severe OHSS, this life threatening complication can still occur in high-risk patients. It would be prudent to avoid hCG luteal rescue and freeze all embryos for future transfer in such women particularly when there are ≥18 follicles with 10-14 mm diameters even with few larger follicles.

Prospective assessment of the impact of endometriomas and their removal on ovarian reserve and determinants of the rate of decline in ovarian reserve.

STUDY QUESTION: Do the presence of endometriomas and their laparoscopic excision lead to a decrease in ovarian reserve as assessed by serum anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER: Both the presence and excision of endometriomas cause a significant decrease in serum AMH levels, which is sustained 6 months after surgery. WHAT IS KNOWN ALREADY: No previous comparison of serum AMH levels between women with and without endometrioma has been reported. However, studies have suggested a decline in serum AMH levels 1-3 months after endometrioma excision but long-term data are needed. STUDY DESIGN, SIZE, DURATION: A prospective cohort study including 30 women with endometrioma >2 cm were age matched with 30 healthy women without ovarian cysts. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with endometrioma underwent laparoscopic excision with the stripping technique. Serum AMH level and antral follicle count (AFC) were determined preoperatively, 1 and 6 months after surgery. Correlation analyses were undertaken in order to identify determinants of surgery-related change in ovarian reserve. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with controls at baseline, women with endometrioma had lower AMH levels (4.2 ± 2.3 versus 2.8 ± 2.2 ng/ml, respectively, P = 0.02) and AFC (14.7 ± 4.1 versus 9.7 ± 4.8, respectively, P < 0.01). Serum AMH levels were further decreased 6 months after surgery (2.8 ± 2.2 versus 1.8 ± 1.3 ng/ml, P = 0.02), while AFC remained unchanged (9.7 ± 4.8 versus 10.4 ± 4.2, P = 0.63). The rate of decline in AMH was not correlated with age, laterality of endometrioma, cyst diameter or the number of primordial follicles on the surgical specimens. The preoperative serum AMH level was positively correlated with the rate of decline in serum AMH after surgery (r = 0.47, P = 0.02). LIMITATIONS, REASONS FOR CAUTION: The absence of a non-treated group of women with endometriomas as a further control prevents comment on the presence of a progressive decline in ovarian reserve related to endometrioma per se. The sample size may be too small for detection of factors correlated with the extent of ovarian damage. WIDER IMPLICATIONS OF THE FINDINGS: While the findings are mostly in agreement with previous studies, the present study is the first to show that the presence of endometrioma per se is associated with a decrease in ovarian reserve. The extent of surgery-related decline in ovarian reserve is not predictable using preoperative or perioperative factors. It may be prudent to measure AMH levels preoperatively and delay/avoid surgical excision as far as is possible if subsequent fertility is a concern. Additional studies are required to further investigate whether the endometrioma-related decline in ovarian reserve per se is progressive in nature and whether it exceeds the surgery-related decline. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Research Fund of the Uludag University School of Medicine. The authors have no conflict of interest associated with this study.

Effect of high-dose estrogen in luteal phase support on live birth rates after assisted reproduction treatment cycles.

OBJECTIVE: The role of estrogen administration for luteal phase support (LPS) after assisted reproductive technologies treatment is not well established. While most studies report ineffectiveness of doses up to 4 mg/day, a small randomized, controlled trial suggested improved clinical outcome with higher dosage of 6 mg/day. The present pilot trial assessed effectiveness of 6 mg/day estrogen in addition to progesterone administration for LPS. STUDY DESIGN: Randomized, controlled trial. Sixty women undergoing assisted reproduction treatment were randomly allocated to receive progesterone vaginal gel with or without 6 mg/day 17beta-estradiol (E2) orally starting from the embryo transfer day. RESULTS: Embryo implantation rates were 33.33% and 28.9% in the control and E2 groups, respectively (p = 0.64). There were 11 (36.7%) live births in the control group, while there were 10 (33.3%) live births in the E2 group (p = 0.79). CONCLUSION: Our results do not suggest a beneficial effect of orally administered estrogen as adjuncts to progesterone for luteal support when administered to all patients in an unselective manner, even in a dose of 6 mg/day.

Medical treatment of uterocutaneous fistula with gonadotropin-releasing hormone agonist administration.

BACKGROUND: Uterocutaneous fistula is a rare complication of uterine surgery. All published cases have been surgically treated with hysterectomy and excision of the fistulous tract. We report a case of uterocutaneous fistula that was successfully treated with gonadotropin-releasing hormone agonist administration. CASE: A 25-year-old woman reported bloody discharge during her periods from a previous Pfannenstiel incision. A fistulous tract leading from the incision scar to the uterus was diagnosed. Leuprolide acetate depot was administered twice subcutaneously at a dose of 11.25 mg. The fistulous tract closed spontaneously, and the patient was symptom free thereafter. CONCLUSION: Medical treatment with gonadotropin-releasing hormone agonists should be considered before resorting to surgery for treatment of uterocutaneous fistulae.

Prevention of adhesion formation following ovarian surgery in a standardized animal model: comparative study of Interceed and double layer Surgicell.

AIM: Comparison of antiadhesive performances of double layer Surgicell and single layer Interceed following ovarian surgery in a rabbit model. METHODS: Prospective randomized controlled trial performed at the animal laboratory of a university. Thirty-nine New Zealand White female rabbits of reproductive age were included. Ovaries were bivalved with a no. 15 scalpel. One of the ovaries was covered with a single layer of Interceed while the other was covered with a double layer of Surgicell. In the control group no adhesion barriers were used. Four weeks later adhesions were scored macroscopically. Following oophorectomy specimens were evaluated microscopically for mesothelial proliferation. The macroscopic adhesion score according to Blauer's criteria and the number of mesothelial cell layers were compared. RESULTS AND CONCLUSION: The control group had significantly higher adhesion scores than the barrier groups. Macroscopic adhesion scores were not different among the barrier groups. The average number of mesothelial cell layers was 1.77+/-2.68, 1.69+/-2.58 (range 0-8) and 2.04+/-2.84 (range 0-10) for ovaries in the control, Interceed and Surgicell groups, respectively: the difference was not significant. Our results demonstrate that a double layer of Surgicell is as effective as Interceed in reducing postoperative adhesion formation in a rabbit model.

Increased progesterone production during the luteal phase of menstruation may decrease anesthetic requirement.

UNLABELLED: Besides having important hormonal effects, progesterone has depressant and hypnotic effects on the brain. In this study, we compared women in the follicular phase with low progesterone levels and in the luteal phase with high progesterone levels regarding their anesthetic requirements. Twenty patients with menstrual cycle days from 1 to 10 (follicular group) and 20 patients with menstrual cycle days from 18 to 24 (luteal group) were included in the study. Anesthesia was induced with fentanyl and thiopental; relaxation was secured with rocuronium, and anesthesia was maintained with a mixture of nitrous oxide 2 L/min and oxygen 2 L/min plus sevoflurane. The delivered sevoflurane concentration was adjusted to sustain a constant bispectral index value that averaged 46 in both groups. To determine the progesterone levels, blood samples were taken from all patients before surgery. We found that progesterone levels were 0.86 +/- 0.30 ng/mL in the follicular group and 7.48 +/- 3.86 ng/mL in the luteal group. The minimum alveolar anesthetic concentration (MAC)-hour (MAC-h) value of sevoflurane in the follicular group (1.55 +/- 0.18 MAC-h) was significantly larger than in the luteal group (1.3 +/- 0.13 MAC-h) (P < 0.0001). The sevoflurane requirements were larger in the follicular group during the maintenance phase of anesthesia. In conclusion, high progesterone levels during the luteal phase might be the cause of decreased anesthetic requirement. IMPLICATIONS: The aim of this study was to determine the effect of high progesterone levels on anesthetic requirement. We measured progesterone levels before surgery and calculated the sevoflurane dose (MAC-h) required to maintain a constant bispectral index value. The dose of sevoflurane correlated inversely with serum progesterone concentrations.