Effect of lesion location on endometriotic adhesion and angiogenesis in SCID mice

Objective

To evaluate the effects of lesion location on adhesion and angiogenesis of transplanted endometriotic lesions in SCID mice.

Methods

Three groups of female SCID mice included intraperitoneal (i.p.) (n = 12), subcutaneous (s.c.) (n = 12), and mock surgery (control) (n = 12). At 2 weeks after ovariectomy, the mice were transplanted with eutopic endometrium from endometriosis patients either subcutaneously or sutured within the peritoneal, or underwent mock surgery. After 4 weeks, the mice were sacrificed to evaluate the adhesion and volume changes of the implanted lesions. Furthermore, semiquantitative immunohistochemical staining was performed to analyze expression of MMP-2 and TIMP-2 as adhesion makers, and vWF, VEGF, and HIF-1α as angiogenesis markers.

Results

Adhesion occurred in 9 of 12 mice in the i.p. group, 3 of 12 mice in the s.c. group, and 3 of 12 mice in the control group. Fisher’s exact test showed that the difference of adhesion occurrence between i.p. and s.c. groups was statistically significant (p < 0.05). Graft volume changes were higher in the s.c. group than those in the i.p. group. MMP-2 expression was higher in the s.c. group than that in the i.p. group (p < 0.01). There was no significant difference of TIMP-2 expression between s.c. and i.p. groups. vWF, VEGF, and HIF-1α expression was significantly higher in the s.c. group than that in the i.p. group (p < 0.01).

Conclusions

Lesion location might be involved in the pathological changes of endometriosis. The intraperitoneal location is related to endometriotic adhesion, whereas the subcutaneous location is related to the infiltration of endometriotic lesions.     

Elevated RON protein expression in endometriosis and disease-associated ovarian cancers

Background

Recepteur d’origine nantais (RON) protein expression has been demonstrated to correlate with tumor progression, metastasis, and prognosis, and its mRNA expression increases in deeply infiltrating endometriotic lesions. However, it remains unclear whether RON protein expression also increases in endometriotic lesions, and may be a risk factor of malignant transformation in endometriotic lesions.

Methods

The protein expression of RON in control (n = 19), eutopic (n = 16), and ectopic (n = 51) endometria, as well as in endometriosis-associated ovarian cancers (EAOC, n = 16) was determined by immunohistochemical (IHC) staining.

Results

Endometriotic lesions expressed low levels of RON protein, but no RON protein expression appeared in matched eutopic or control endometrium. EAOC exhibited high levels of RON protein. The frequency and IHC score of RON protein expression were both significantly higher in EAOC [100.0% (14/14), 5.37 ± 0.74] than those in endometriotic lesions [51.0% (26/51), 2.15 ± 1.12; P = 0.002, 0.001]. Multivariate analysis of covariance only revealed a correlation of RON protein expression and EAOC (P = 0.006), but no correlations of RON protein expression and clinical parameters (P > 0.05).

Conclusions

These obtained results suggest that increased RON expression might be involved in the pathogenesis of endometriosis and disease-associated ovarian cancers.

     

Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in a rat endometriosis model

Purpose

The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis.

Methods

Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups.

Results

Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05).

Conclusion

Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosis through its anti-inflammatory and anti-nociceptive properties.     

Ovarian stripping versus cystectomy: recurrence of endometriosis and pregnancy rate

Purpose

To compare two different surgical techniques, stripping or cystectomy, in patients treated with the same post-operative medical therapy in terms of recurrence of endometrioma, recurrence of pain and spontaneous pregnancy rate within 2 years from surgery.

Methods

The inclusion criteria of this study were: (1) 25–40 years old; (2) ovarian endometrioma more than 3 cm of diameter detected by transvaginal ultrasonography (3) regular menstrual cycle (4) post-operative treatment with GnRH analogs, (5) tubal patency assessed by laparoscopic chromopertubation (6) normal human semen characteristics. Exclusion criteria were uterine myoma, previous medical treatment for endometriosis, presence of adenomyosis, previous surgery of ovarian endometrioma, multiple cysts, bilateral involvement, co-existence of deep endometriosis. Patients were assigned to two study groups: group A (N = 45) patients undergoing stripping technique and group B (N = 64) patients undergoing cystectomy technique for ovarian endometrioma.

Results

In group B the percentage of ultrasonographic recurrence (15.4 %, N = 15) is much lower than in group A (55.6 %, N = 25). (p value 0.001). In group B the percentage of symptomatic recurrence (21.8 %, N = 14) is much lower than in group A (53.3 %, N = 24) (p value 0.001). Spontaneous pregnancy rate in group A patients was of 4.4 % (N = 2) and in group B 22.3 % (N = 21), (p value 0.0072). However, the percentage of specimen with adjacent healthy ovarian tissue was lower in group A (26.6 %) than in group B (50 %) (p value 0.01).

Conclusions

Among the different treatment options for surgical treatment of ovarian endometrioma, in our experience cystectomy appears to be the most appropriate treatment, both in terms of recurrence and pregnancy rate.     

The relation of pelvic pain and dense adhesions to Doppler ultrasound findings in patients with ovarian endometriomas

Purpose

To study the relation of pelvic pain symptoms and pelvic adhesions to Doppler ultrasound findings in patients with ovarian endometriomas.

Methods

62 patients who underwent laparoscopic surgery for endometrioma were divided into two groups according to their pelvic pain symptoms. Group 1 (n = 27) included patients with pelvic pain, group 2 (n = 35) asymptomatic patients. Patients were evaluated for the vascularization of endometrioma by transvaginal color and power Doppler ultrasonography before the surgery. The presence and amount of blood flow reported in terms of a color scale, pulsed Doppler indices, and dense pelvic adhesions were compared between the groups. The relation of Doppler ultrasound findings to the dense pelvic adhesions was also analyzed.

Results

Blood flow was present in 74.1 % (n = 20) of patients in group 1 and 68.6 % (n = 24) in group 2 (p = 0.63). The volume and vascularization of the endometriomas, pulsed Doppler indices, stage of endometriosis, and the presence of dense pelvic adhesions were also similar. Patients with dense pelvic adhesions had significantly higher amount of blood flow compared to patients without adhesions (p = 0.006), but the mean pulsatility index and resistance index were not different between the groups (p = 0.55 and 0.59, respectively).

Conclusions

Pelvic pain symptoms were not found to be related to endometrioma vascularization. On the other hand, we observed an association between higher vascularized endometrioma and the presence of dense pelvic adhesions.     

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis

Purpose

To determine, with extended receiver operating characteristic (ROC) curve analysis, the diagnostic value of cytokines showing significantly different peritoneal concentrations between women with and without endometriosis.

Methods

Multiplex cytokine concentration measurement of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ levels in peritoneal fluid of women with minimal to mild (n = 10) and moderate to severe (n = 26) endometriosis, and 42 controls.

Results

Only IL-6 and IL-10 concentrations were significantly higher in endometriosis patients than in controls. Specifically, significantly higher IL-6 and IL-10 levels were found in moderate to severe but not in minimal to mild endometriosis as compared to controls. For evaluation of diagnostic significance, ROC analysis determined discriminating parameters for IL-6, while those calculated for IL-10 were useless. Importantly, ROC analysis for IL-6 levels limited to women with moderate to severe endometriosis showed the highest area under the curve with the sample size sufficient to achieve 90 % power of the test. Finally, extended ROC including cost of analysis for this group of patients determined the optimal cut-off leading to high specificity and positive likelihood ratio resulting in 79 % effectiveness of the test.

Conclusions

While our outcomes show moderate usefulness of peritoneal IL-6 levels in discrimination of moderate to severe endometriosis, further studies might be needed to determine the usefulness of peritoneal IL-6 levels in detection of early stages of endometriosis, as such a finding would be more relevant in clinical decision making.     

Prophylactic pre-operative bilateral ureteric catheters for major gynaecological surgery

Purpose

The use of prophylactic pre-operative bilateral ureteric catheters for major gynaecological surgery is controversial. The aim of this study was to investigate the frequency of ureteric catheter-associated morbidity in our Unit, where systematic pre-operative ureteric catheterisation is performed.

Methods

We conducted a retrospective casenote review of 337 gynaecology patients undergoing laparotomy at Salford Royal Hospital between January 2007 and September 2010.

Results

The mean age was 56.36 (range 17–89). Procedures included TAH BSO (n = 249, 74 %), BSO (n = 17, 5 %), radical hysterectomy (n = 36, 11 %), and other (n = 35, 10 %), for indications of ovarian (n = 189, 56 %), uterine (n = 88, 26 %) or cervical cancer (n = 18, 5.3 %), massive fibroids (n = 27, 8 %), severe endometriosis (n = 6, 1.78 %), or other (n = 9, 2.67 %). Bilateral ureteric catheters were attempted in most patients and successfully placed in 315/337 (93 %) patients. In 22 patients (7 %), either no ureteric catheters or a single ureteric catheter was placed due to pre-existing ureteric anomaly, technical difficulty, or surgeon choice. Bilateral ureteric catheterisation took an average of 5.4 min (SD 2.0, range 3.2–9.2) for an experienced consultant or 8.4 min (SD 3.9, range 6.4–18.6) for an SpR trainee to complete. There were no intra-operative ureteric complications. Post-operative complications included urinary tract infection (5/337 patients, 1.48 %), acute renal failure (2/337, 0.6 %), and uretero-vaginal fistulae (1/337 patients, 0.3 %).

Conclusions

Prophylactic pre-operative ureteric catheters are quick and easy to insert and associated with low complication rates. Routine use before major gynaecological surgery can expedite intra-operative identification of the ureters and may reduce accidental ureteric injury.     

Non-assessable endometrium in women with post-menopausal bleeding: to investigate or ignore

Background

In women presenting with post-menopausal bleeding (PMB), the incidence of endometrial cancer is 1–10 %; Trans-vaginal scan (TVS) is offered as the first line of investigation to triage women further and a thick endometrium (>4 mm) merits endometrial tissue sampling for further evaluation. When it is difficult and not possible to assess the endometrium sonographically, decision to investigate further lies with the clinician.

Aim

Study outcomes for women with PMB and endometrium not assessable on TVS.

Methods

We collected data retrospectively between September 2007 and December 2010. We identified our study group from the radiology database. Data collected include ultrasound findings, methods of endometrial sampling, and the result of cytology/histology.

Results

In our study period of 40 months, 671 women with post-menopausal bleeding were referred to the ultrasound department for TVS to assess endometrial thickness. 92 % (614/671) women had the assessment. In 57 women (8 %), endometrial thickness was not assessable and this formed our study group. 3/57 records were not retrievable and excluded from our study. 43/54 (79 %) had some form of endometrial sampling done. Among the 81 % adequate samples (35/43), 7 (20 %) had endometrial cancer; 1 (3 %) had CAH, 1 (3 %) was diagnosed with cervical cancer. In women who had thickened endometrium (>4 mm; n = 448), there were 29 cases of endometrial cancers detected giving an incidence of 6.4 %. In women with PMB and non-assessable endometrial thickness, there is increased incidence of endometrial cancer when compared to the group where endometrial thickness could be measured. (Odds ratio = 3.3 [95 % CI = 1.2–9]). This is a statistically (p = 0.017) and clinically significant finding.

Conclusion

In women with PMB, there will be a subgroup in which ultrasound cannot assess endometrial thickness. When compared to women where endometrial thickness is measurable, this group stands a higher risk of endometrial cancer and hysteroscopy/ hysterosonography with endometrial sampling is recommended in this group.     

Combination of non-invasive and semi-invasive tests for diagnosis of minimal to mild endometriosis

Objectives

Non-surgical diagnostic approach for endometriosis would be of great gain to both physicians and patients. The aim of this study was to evaluate the diagnostic value of serum measurement of IL-6 combined with the presence of nerve fibres in the functional layer of endometrium for diagnosis of minimal-mild endometriosis.

Methods

In this prospective study 114 women who underwent laparoscopy for infertility and/or pelvic pain were divided into two groups: control cases (40 cases) with no pathologic findings; and endometriosis patients (74 cases) [subdivided into stages 1–2 or minimal-mild (MM) and stages 3–4 or moderate-severe cases]. Blood was drawn one day before laparoscopy and stored for subsequent analysis of IL-6. Endometrial biopsy was obtained prior to laparoscopy and Immunohistochemistry was performed using the pan-neuronal marker protein gene product 9.5(PGP9.5). Then laparoscopic diagnosis of endometriosis confirmed by histopathology was done.

Results

Serum IL-6 with a threshold of 15.4 pg/ml was found to be able to diagnose MM endometriosis with 89.5 % sensitivity and 82.5 % specificity, but sensitivity and specificity of presence of nerve fibres in the functional layer of endometrium were 92 % and 80 % respectively. When two diagnostic modalities were combined the sensitivity and specificity were raised to 100 and 92.5 % respectively.

Conclusions

Combination of both serum IL-6 and presence of nerve fibres in the endometrium is more reliable method for diagnosis of MM endometriosis than in single test.     

Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis

Purpose

The current study investigated the potential therapeutic efficiency of atosiban, an oxytocin receptor antagonist, in an experimental endometriosis model.

Methods

Endometriosis was surgically induced in 35 female rats during estrus. Four weeks after this procedure, relaparotomy was performed. The viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups. In the first group (n?=?8), a daily dose of 0.2?ml 0.9?% NaCl was injected intraperitoneally (i.p.) (control cases). In the second and third groups (n?=?8 and n?=?8), 0.5?mg/kg/day i.p. atosiban and 1?mg/day i.p. diltiazem were given, respectively. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriosis foci were recorded. The endometrial implants were processed for histological and immunohistochemical studies. The volumes of endometriotic implants were measured, and immunohistochemical analyses were performed, and compared between the groups.

Results

After the treatment with atosiban, volumes of endometriotic implants decreased significantly. Proliferating cell nuclear antigen expression levels were significantly reduced in the atosiban and diltiazem groups compared with the control group.

Conclusions

In a rat endometriosis model, atosiban, an agent used for the first time for the medical treatment of endometriosis, has shown significant therapeutic efficiency.     

Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis

Background

Reported associations of progesterone receptor gene polymorphism (PROGINS) with endometriosis have been inconsistent.

Aim of the study

To evaluate the association between the PROGINS polymorphism and the risk of endometriosis.

Methodology

A meta-analysis of 12 published case–control studies with a total sample size of 3,321 (1,323 cases/1,998 controls) was performed. We estimated the risk (odds ratio [OR] 95 % confidence intervals) of endometriosis association with the PROGINS polymorphism.

Results

An association between the presence of the variant allele and risk of endometriosis was found, more in the homozygous and recessive models (OR 1.41–1.43, p = 0.15–0.17), and less in the dominant and co-dominant models (OR 1.22, p = 0.11–0.15). Reanalysis without the studies whose controls deviated from the Hardy–Weinberg Equilibrium did not materially alter the dominant and co-dominant effects (OR 1.19–1.22, p = 0.19–0.32), but exacerbated the homozygous and recessive effects (OR 1.59, p = 0.09). The subgroups based on geography showed increased risk associations, consistently significant in the European (OR 1.52–2.72, p = 0.0008–0.03) but not in the Brazilian studies, where ORs ranged from reduced (OR 0.70–0.74, p = 0.54–0.61) to increased (OR 1.11, p = 0.75) risks. Heterogeneity was confined in all comparisons to the dominant and co-dominant models (I ² = 38–70 %), except in the European subgroup, which had zero heterogeneity (I ² = 0 %) in all genetic models, as did all homozygous and recessive effects.

Conclusion

This meta-analysis provides a comprehensive profile of the role of the PROGINS polymorphism in endometriosis by exploring the magnitude of the summary effects with modifier analysis. This magnitude is expressed with modulation or exacerbation of the summary effects, as defined by the parameters of the analysis. Thus, the results showed trend towards an increased risk of the variant PROGINS allele and susceptibility for the endometriosis.     

Deep endometriosis inflicting the bladder: long-term outcomes of surgical management

Objective

To assess the efficacy and safety of laparoscopic treatment of bladder endometriosis, especially in cases of full thickness endometriotic nodules.

Design

Retrospective review of medical records.

Setting

Tertiary medical center and a referral center for endometriosis.

Population

Sixty-nine patients with bladder endometriosis that underwent surgery between January 2005 and December 2011.

Methods

The records of all patients with bladder endometriosis were reviewed and the pre-, intra- and postoperative information of patients who underwent surgery was collected.

Main outcome measures

Efficacy, safety and long-term outcome of laparoscopic treatment of bladder endometriosis.

Results

The mean age of 69 patients with bladder endometriosis was 31.3 ± 4.6 years. Preoperative urinary symptoms (such as frequency, urgency, dysuria and others) were present in 28 (40.0 %) patients. Laparoscopy was performed in all patients. Deep detrusor involvement was found in 45 (65.2 %) patients. Of these, 21 patients underwent partial cystectomy due to a full thickness lesion. Deep nodule resection without bladder invasion was performed in 24 (34.8 %) patients and bladder nodule coagulation and ablation in the remaining 24 (34.8 %) patients with superficial involvement. No intraoperative complications were noted. Postoperative follow-up results were available for all patients. After a median (range) follow-up period of 60 (4–92) months, 92.7 % of the patients were asymptomatic or reported improvement in symptoms.

Conclusions

After a long-term follow-up surgical management of bladder endometriosis is strongly recommended. During surgery, careful inspection and full excision of bladder lesions should be performed. Laparoscopic excision is a safe and efficacies approach.     

Expression of human β-defensin-2 in the eutopic and ectopic endometrial tissues in patients with endometriosis

Objective

To investigate the expression of human β-defensin-2 (hBD-2) in the endometrium of patients with endometriosis (EMS) and explore the potential role of hBD-2 in the pathogenesis of EMS.

Design

Prospective controlled study.

Sample

50 women including EMS patients undergoing laparoscopic ovarian cystectomy and non-EMS patients undergoing hysterectomy for uterine fibroids.

Setting

Large university teaching hospital.

Methods

Patients were divided into EMS and non-EMS groups. The gene expressions of hBD-2, interleukin (IL)-1β and tumor necrosis factor (TNF)-α in the endometrial tissues of each group were detected with real-time quantitative polymerase chain reaction (PCR), and hBD-2 protein expression with immunohistochemical method.

Results

The gene expression levels of hBD-2, TNF-α, and IL-1β as well as the positive expression rate of hBD-2 protein in the ectopic endometrium of EMS patients were significantly higher than those in the eutopic endometrium of EMS and non-EMS patients (all P < 0.05). Correlation analysis showed that the gene expression levels of hBD-2 in the ectopic and eutopic endometrium of EMS patients were positively correlated with the gene expression levels of IL-1β and TNF-α (P < 0.01).

Conclusion

High levels of hBD-2 gene and protein expressions in the ectopic endometrium of EMS patients may be an important contributor in the pathogenesis of EMS. TNF-α and IL-1β may promote the upregulation of hBD-2 expression.     

The sequence of intrapartum interventions: a descriptive approach to the cascade of interventions

Purpose

To model the timing and sequence of intrapartum interventions and to estimate the association with labor length and delivery mode.

Methods

A longitudinal multi-center cohort study included data from 3,955 low-risk women who gave birth in hospitals in Lower Saxony, Germany. We analyzed three intrapartum interventions: amniotomy, oxytocin augmentation and epidural analgesia. We divided births into time intervals delineated by these interventions and noted cervical dilation at interval onset. We analyzed the duration of intervals from onset of labor until the first intervention and between intrapartum interventions with Kaplan–Meier’s estimate, regarding the three interventions as competing risks. Further, we analyzed the cervical dilation before an intervention by Kaplan–Meier’s estimate without censoring.

Results

73.2 % of the included 2,082 nulliparae (n = 1,525) and 59.6 % of the included 1,873 multiparae (n = 1,117) received at least one intervention, while 1,313 women (33.2 %) experienced a normal labor without any of these interventions. The intervals from onset of labor until the first intervention and from the first until the second intervention were significantly shorter in multiparae than in nulliparae. The intervention cascade in nulliparae most often started with epidural analgesia in early labor (n = 579, 27.8 %). Oxytocin augmentation most often followed after a short interval (n = 343, 59.2 %, median 1.57 h). In multiparae, amniotomy was most often the first intervention (n = 629, 33.6 %), and spontaneous birth most often followed (n = 503, 80.0 %). Labor duration and operative deliveries increased as interventions increased.

Conclusions

The temporal sequence of intrapartum interventions varied in association with parity, cervical dilation, labor duration and mode of birth.     

Interferon stimulated gene 15 expression at the human embryo−maternal interface

Purpose

In early pregnancy the dialogue between maternal endometrium and embryo is a key process in establishing a receptive decidua and placental network. Decidual ISG15 induction is thought to promote pregnancy maintenance and development. ISG15 is involved in RNA splicing, cytoskeletal organization, stress response and further intracellular processes.

Methods

ISG15 expression was examined immunohistologically in paraffin-embedded human placental and decidual tissue samples of all pregnancy trimesters on adjacent sections (first trimester n = 5, second n = 5, third n = 3). Samples were processed using a protocol applying a rabbit polyclonal ISG15 antibody. A mouse monoclonal cytokeratin seven antibody was utilized to identify the different placental departments and decidual glands. Staining results and anatomical features were evaluated blindly with strict rating criteria.

Results

ISG15 expression was identified in first and second trimester tissue samples. ISG15 localized especially to the extravillous cytotrophoblasts in the maternal wall and in maternal blood vessel. Expression was detected in cytotrophoblast progenitor cells in the placental villi and the cell column with a maximum in the first trimester. The syncytial layer stained positive in first and second trimester samples. Third trimester samples showed no expression of ISG15 at all.

Conclusions

ISG15 abundance in the human placenta is an interesting finding, with implications for placental development, fetal growth and potential defense mechanism against infections. The maximal expression of ISG15 in the first and second trimester of pregnancy suggests that ISG function is needed when placental and embryo development is enormous and embryo susceptibility to external influences is high.     

The role of apoptosis in preterm premature rupture of the human fetal membranes

Purpose

The present study was designed to examine apoptotic cell death via the caspase-dependent pathway in human fetal membranes.

Methods

Amniotic membrane samples were collected from three groups of women: group 1, women with preterm premature rupture of fetal membranes (PPROM) after cesarean delivery (n = 10), group 2, women with preterm labor (PTL) with intact membranes after cesarean delivery (n = 9) and group 3, women with term labor and vaginal delivery after an uncomplicated pregnancy (controls) (n = 11).

Results

Active caspase-3 immunopositivity (ACPI) of the PPROM group was significantly higher than that of the control group (p < 0.05). ACPI was higher in the PTL with intact membranes group as compared to the control group; however, it did not reach statistical significance (p > 0.05).

Conclusion

Active caspase-3 positivity is increased in the fetal membranes of those women with PPROM.     

Factors associated with a poor prognosis for the IVF-ICSI live birth rate in women with rAFS stage III and IV endometriosis

Purpose

To assess the factors associated with a poor prognosis for a cumulative IVF live birth rate (LBR) in women with stage III and IV endometriosis according to the revised classification of the American Fertility Society (rAFS).

Methods

A retrospective cohort study was conducted between January 1, 2010, and December 31, 2014, in our Reproductive Medicine Center. We analyzed different factors associated with a poor prognosis for a cumulative IVF LBR in women with rAFS stage III and IV endometriosis. A total of 101 patients were included, representing 232 IVF-ICSI cycles and 212 embryo transfers. The primary endpoint was the cumulative LBR per cycle and per patient.

Results

The cumulative LBR per cycle was 14.7% (n = 34) and that per patient was 31.7% (n = 32). The cumulative LBR was significantly decreased by active smoking [_adjOR = 3.4, 95% CI (1.12–10.60), p = 0.031], poor ovarian response (POR) according to the Bologna criteria [_adjOR = 11.5, 95% CI (1.37–96.83), p = 0.024], and rAFS stage IV [_adjOR = 3.2, 95% CI (1.13–8.95), p = 0.024]. The cumulative LBR per women was 59.4% without factors associated with a poor prognosis and 25.6% in the case of one factor, and it decreased to 7.7% in the case of two or three factors (p < 0.001).

Conclusion

Active smoking, POR according to the Bologna criteria, and rAFS stage IV endometriosis had a negative impact on the IVF-ICSI cumulative LBR for women with rAFS stage III and IV endometriosis. Because smoking dramatically decreases the LBR with endometriosis, stopping smoking before IVF-ICSI should be strongly advised.