Publication
Trew G, Pistofidis G, Pados G, Lower A, Mettler L, Wallwiener D, Korell M, Pouly JL, Coccia ME, Audebert A, Nappi C, Schmidt E, McVeigh E, Landi S, Degueldre M, Konincxk P, Rimbach S, Chapron C, Dallay D, Röemer T, McConnachie A, Ford I, Crowe A, Knight A, Dizerega G, Dewilde R
• 08/2011
BACKGROUND: Gynaecological laparoscopic surgery outcomes can be compromised by the formation of de novo adhesions. This randomized, double-blind study was designed to assess the efficacy and safety of 4% icodextrin solution (Adept(®)) in the reduction of de novo adhesion incidence compared to lactated Ringer's solution (LRS). METHODS: Patients undergoing laparoscopic surgery for removal of myomas or endometriotic cysts were treated with randomized solution as an intra-operative irrigant and 1l post-operative instillate. De novo adhesion incidence (number of sites with adhesions), severity and extent were independently scored at a second-look procedure and the efficacy of the two solutions compared. The effect of surgical covariates on adhesion formation was also investigated. Initial exploratory analysis of individual anatomical sites of clinical importance was progressed. RESULTS Of 498 patients randomized, 330 were evaluable (160 LRS--75% myomectomy/25% endometriotic cysts; 170 Adept--79% myomectomy/21% endometriotic cysts). At study completion, 76.2% LRS and 77.6% Adept had ≥ 1 de novo adhesion. The mean (SD) number of de novo adhesions was 2.58 (2.11) for Adept and 2.58 (2.38) for LRS. The treatment effect difference was not significant (P = 0.909). Assessment of surgical covariates identified significant influences on the mean number of de novo adhesions regardless of treatment, including surgery duration (P = 0.048), blood loss in myomectomy patients (P = 0.019), length of uterine incision in myomectomy patients (P < 0.001) and number of suture knots (P < 0.001). There were 15 adverse events considered treatment-related in the LRS patients (7.2%) and 18 in the Adept group (8.3%). Of 17 reported serious adverse events (9 LRS; 8 Adept) none were considered treatment-related. CONCLUSIONS: The study confirmed the safety of Adept in laparoscopic surgery. The proportion of patients with de novo adhesion formation was considerably higher than previous literature suggested. Overall there was no evidence of a clinical effect but various surgical covariates including surgery duration, blood loss, number and size of incisions, suturing and number of knots were found to influence de novo adhesion formation. The study provides direction for future research into adhesion reduction strategies in site specific surgery.
Publication
De Ziegler D, Streuli MI, Borghese B, Bajouh O, Abrao M, Chapron C
• 08/2011
Endometriosis causes pelvic pain and infertility. Infertility results from effects of endometriosis exerted in the pelvic cavity, in the ovaries and/or on the uterus. Medical treatment effective on pain and at preventing disease recurrence following surgery is of no use for improving the chances of conceiving naturally. Surgery however improves the chances of conceiving in the 12-18 months afterward. Endometriosis through extension of the disease to the ovaries may harm ovarian response to COS needed in ART. Surgery for endometrioma(s) may further reduce ovarian responses to COS in case of endometriosis. Remarkably however, reduced ovarian responses due to endometriosis are not necessarily associated with reduced oocyte quality and ART outcome. Pre-ART treatment with oral contraceptives (OC) improves ART outcome in case of ovarian endometriosis particularly, if endometriomas are present at the time of oocyte retrieval. This measure requires however that a proper OC-FSH/hMG interval is respected and that -'LH-' effects are provided during the ovarian stimulation, using either hMG or small doses of hCG. These latter precautions prevent the adverse outcome reported in case of pre-ART use of OC when ovarian stimulation is conducted using r-FSH exclusively.
Publication
Chapron C, Souza C, Borghese B, LafayPillet MC, Santulli P, Bijaoui G, Goffinet F, de Ziegler D
• 08/2011
BACKGROUND: The relationship between the use of oral contraception (OC) and endometriosis remains controversial. We therefore compared various characteristics of OC use and the surgical diagnosis of endometriosis histologically graded as superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) or deep infiltrating endometriosis (DIE). METHODS: This cross-sectional study included 566 patients without visible endometriosis at surgery as controls, and 410 patients with histologically proven endometriosis, categorized by their worst lesions as SUP n = 47, OMA n = 120 and DIE n = 243. Personal data, including on OC use, were prospectively collected during standardized interviews. Statistical analysis was performed using unconditional logistic regression. RESULTS: Past OC users had an increased incidence of endometriosis (adjusted odd ratios (OR) = 2.79, 95% confidence interval (CI) 1.74-5.12, P = 0.002) of any revised American Fertility Society stage. Women who had previously used OC for severe primary dysmenorrhea were even more frequently diagnosed with endometriosis (adjusted OR = 5.6, 95% CI 3.2-9.8), especially for DIE (adjusted OR = 16.2, 95% CI 7.8-35.3). Women who had previously used OC for other reasons also had an increased risk of endometriosis, but to a lesser extent (adjusted OR = 2.6, 95% CI 1.8-4.1). The age at which OC was initiated, duration of OC use and free interval from last OC use were not significantly different between control and endometriosis women, irrespective of histological grading. Current OC users did not show an increased prevalence of endometriosis (OR = 1.22, 95% CI 0.6-2.52). CONCLUSIONS: Our data indicate that a history of OC use for severe primary dysmenorrhea is associated with surgical diagnosis of endometriosis, especially DIE, later in life. However, this does not necessarily mean that use of OC increases the risk of developing endometriosis. Past use of OC for primary dysmenorrhea may serve as a marker for women with endometriosis and DIE.
Publication
Noël JC, Anaf V, Borghese B, Vaiman D, Fayt I, Chapron C
• 06/2011
Steroidogenic factor-1 (SF-1) protein expression was not observed in any form of endometriosis (peritoneal, ovarian, or deep infiltrating endometriosis), which suggests that SF-1 locally produced by endometrial or stromal cells may not play a major role in the development of endometriosis. However, the strong expression of SF-1 in cortical and medullary ovarian mesenchymatous cells may be capable of creating a favorable steroidogenic environment and the development of the disease.
Publication
Noël JC, Chapron C, Borghese B, Fayt I, Anaf V
• 05/2011
Endometriosis is an enigmatic disease of unknown etiology and pathogenesis, which is defined as the presence of endometrial glands and stroma outside the uterus. The most widely accepted theory to explain endometriosis is probably the transplantation of an endometrial fragment during menstruation to ectopic sites, but the development of endometriosis is extremely complex and includes the adherence to the peritoneal surface and secondary invasion of the underlying tissues. In this study, we have investigated the potential role of galectin-3 (gal-3), a member of a group of carbohydrate-binding proteins, which plays a major role in cell adhesion, migration, angiogenesis, and invasion. The expression of gal-3 has been carried out by immunohistochemistry, according to the different phases of cycle in 50 cases of endometriosis (peritoneal endometriosis: n=10; ovarian endometriosis: n=10; deeply infiltrating endometriosis: n=30) and in 34 cases of eutopic endometrium (10 without endometriosis and 24 with endometriosis). In the proliferative and secretory phases of the cycle, the nuclear and membranous gal-3 expression was higher, first in each variant of the endometriosis than in the eutopic endometrium (P<0.05), and second in the eutopic endometrium of women with endometriosis than in eutopic endometrium of women without endometriosis. Our data suggest that gal-3 may have a potential role in the development of endometriosis.
Publication
de Ziegler D, de Mouzon J, Fauque P, Zanette M, Marszałek A, Blanchet V, Boissonas CC, Wolf JP, Chapron C
• 04/2011
OBJECTIVE: To review donor-egg assisted reproductive technology (ART) activity using young fertile donors (<37 years of age) paired with multiple recipients. DESIGN: Age-matched cohort study. SETTING: Tertiary ART center at Cochin Hospital, Paris. PATIENT(S): A total of 125 oocyte donors and 361 age-matched control subjects. Donated oocytes were attributed to 163 different recipients undertaking 258 transfer cycles. INTERVENTION(S): Donor-egg and regular ART. MAIN OUTCOME MEASURE(S): Controlled ovarian hyperstimulation (COH) outcome-oocytes provided-was compared in donors and control subjects. Clinical pregnancy (cPR), ongoing pregnancy (oPR), and implantation (IR) rates per transfer in recipients were compared with age-matched controls. IRs were analyzed in the various recipients as a function of the number of oocytes harvested. RESULT(S): COH outcome was similar in donors and control subjects. cPR (37.5%), oPR (28.4%), and IR (24.4%) were slightly but significantly lower in donor-egg recipients compared with control subjects (44.9%, 37.4%, and 31.8%, respectively). More embryos (average +2.06) were transferred fresh and fewer frozen. In recipients, IRs were independent from the number of oocytes received in the donor. CONCLUSION(S): Multiplying recipients paired with oocyte donors slightly lowered per-transfer outcome, but enabled more (average +2.06) embryos to be transferred fresh.
Publication
Chapron C, LafayPillet MC, Monceau E, Borghese B, Ngô C, Souza C, de Ziegler D
• 03/2011
OBJECTIVE: To investigate whether the clinical history, particularly of the adolescence period, contains markers of deeply infiltrating endometriosis (DIE). DESIGN: Cross-sectional study. SETTING: Universitary tertiary referral center. PATIENT(S): Two hundred twenty-nine patients operated on for endometriosis. Endometriotic lesions were histologically confirmed as non-DIE (superficial peritoneal endometriosis and/or ovarian endometriomas) (n = 131) or DIE (n = 98). INTERVENTION(S): Surgical excision of endometriotic lesions with pathological analysis of each specimens. MAIN OUTCOME MEASURE(S): Epidemiological data, pelvic pain scores, family history of endometriosis, absenteeism from school during menstruation, oral contraceptive (OC) pill use. RESULT(S): Patients with DIE had significantly more positive family history of endometriosis (odds ratio [OR] = 3.2; 95% confidence interval [CI]: 1.2-8.8) and more absenteeism from school during menstruation (OR = 1.7; 95% CI: 1-3). The OC pill use for treating severe primary dysmenorrhea was more frequent in patients with DIE (OR = 4.5; 95% CI: 1.9-10.4). Duration of OC pill use for severe primary dysmenorrhea was longer in patients with DIE (8.4 ± 4.7 years vs. 5.1 ± 3.8 years). There was a higher incidence of OC pill use for severe primary dysmenorrhea before 18 years of age in patients with DIE (OR = 4.2; 95% CI: 1.8-10.0). CONCLUSION(S): The knowledge of adolescent period history can identify markers that are associated with DIE in patients undergoing surgery for endometriosis.
Publication
Leroyer S, Vatier C, Kadiri S, Quette J, Chapron C, Capeau J, Antoine B
• 02/2011
Glyceroneogenesis, a metabolic pathway that participates during lipolysis in the recycling of free fatty acids to triglycerides into adipocytes, contributes to the lipid-buffering function of adipose tissue. We investigated whether glyceroneogenesis could be affected by human immunodeficiency virus (HIV) protease inhibitors (PIs) responsible or not for dyslipidemia in HIV-infected patients. We treated explants obtained from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) depots from lean individuals. We observed that the dyslipidemic PIs nelfinavir, lopinavir and ritonavir, but not the lipid-neutral PI atazanavir, increased lipolysis and decreased glyceroneogenesis, leading to an increased release of fatty acids from SAT but not from VAT. At the same time, dyslipidemic PIs decreased the amount of perilipin and increased interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) secretion in SAT but not in VAT. Parthenolide, an inhibitor of the NFκB pathway, counteracted PI-induced increased inflammation and decreased glyceroneogenesis. IL-6 (100 ng) inhibited the activity of phosphoenolpyruvate carboxykinase, the key enzyme of glyceroneogenesis, in SAT but not in VAT. Our data show that dyslipidemic but not lipid-neutral PIs decreased glyceroneogenesis as a consequence of PI-induced increased inflammation in SAT that could have an affect on adipocytes and/or macrophages. These results add a new link between fat inflammation and increased fatty acids release and suggest a greater sensitivity of SAT than VAT to PI-induced inflammation.
Publication
Santulli P, Gayet V, Fauque P, Chopin N, Dulioust E, Wolf JP, Chapron C, de Ziegler D
• 02/2011
OBJECTIVE: To review 5 years of assisted reproductive treatments (ART) provided to couples affected by human immunodeficiency virus (HIV). DESIGN: Age-matched cohort study. SETTING: University-based tertiary center. PATIENT(S): Couples in whom the male (n = 87), female (n = 57), or both (n = 17) partners were HIV infected. The first ART cycle was compared with three sets of age-matched control subjects (3-to-1) which included 261, 171, and 51 couples, respectively. INTERVENTION(S): ART in HIV-infected couples and age-matched controls. MAIN OUTCOME MEASURE(S): Infertility duration and ART outcome. RESULT(S): When initiating ART, all three HIV-infected groups had longer infertility histories, computed from when conception was attempted or infertility diagnosed, compared with noninfected age-matched control subjects. Outcome, however, was not different when only the male or female partner was infected, though with a trend toward higher cancellation and lower pregnancy rates. When both partners were HIV infected, cancellation were higher and pregnancy rates lower (12% versus 41.2%), than in age-matched control subjects. CONCLUSION(S): Our data showed longer infertility histories in all HIV-infected couples when undertaking their first ART. Outcome, however, was not altered when only one partner--male or female--was HIV infected. Efforts should therefore aim at assuring that HIV-infected couples access ART as promptly as their noninfected counterparts.
