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Determination of antiovarian antibodies after laparoscopic ovarian electrocauterization in patients with polycystic ovary syndrome
Abstract
To determine whether ovarian damage consequent to laparoscopic ovarian electrocauterization may result in the development of humoral autoimmunity and production of antiovarian antibodies (AOA).
Prospective study.
Infertility and gynecologic endoscopy units of one of the medical university hospitals.
Sixty-four reproductive-age infertile women (<or=35 y of age) with clomiphene citrate-resistant polycystic ovary syndrome (PCOS) and 50 fertile, healthy, reproductive-aged women (<or=35 y of age) as control group.
Laparoscopic ovarian electrocauterization was performed under general anesthesia in clomiphene citrate-resistant PCOS patients for treatment of infertility.
Serum samples from 52 patients (before and about 30-40 days after operation) and from 50 fertile healthy controls were assayed for determination of immunoglobulin class-specific AOA (IgM, IgG, and IgA) by using a commercially available ELISA kit that used human ovary as antigen.
A trend of rising in the level of AOA in all isotypes, IgM, IgG, and IgA, was found in sera after operation, compared with the case of sera obtained before operation. But when the ELISA value was calculated according to the formula recommended by the manufacturer, none of the patients were positive for AOA before the surgical intervention, and none of them developed positive AOA after operation. The overall ovulation rate was 81.3%, and the pregnancy rate was 67.2%.
The ovarian trauma consequent to laparoscopic ovarian electrocauterization in patients with resistant PCOS does not result in a significant production of AOA.
... It is also postulated that inflammation causes alterations of normal antigens to abnormal ones which stimulate immune system to produce anti-ovarian antibodies. In this regards Alborzi et al. [7] examined this hypothesis by measuring anti-ovarian antibodies (AOA) in clomiphen-resistant PCOS patients before and after ovarian elecrocauterization. However, they found that this laparoscopic procedure does not result in increased levels of AOA. ...
... The mechanism of ovulation induction following electrocauterization is unclear. However, several studies have demonstrated its efficacy in treatment of infertility in PCOS [7,13]. Peritubal adhesion leading to infertility is the most important complication of this procedure being studied to a great extend [5,6]. ...
... It is also postulated that inflammation causes alterations of normal antigens to abnormal ones which stimulate immune system to produce anti-ovarian antibodies (AOA). In this regards Alborzi et al. [7] examined this hypothesis by measuring AOA in clomiphen-resistant PCOS patients before and after ovarian elecrocauterization. They included 64 infertile patients with clomiphen citrate-resistant PCOS and 50 healthy fertile subjects as control group. ...
To determine the serum levels of anti-dsDNA, anti-histone, and anti-nucleosome antibodies after laparoscopic ovarian electrocauterization in patients with polycystic ovarian syndrome (PCOS).
Our study was performed on 35 patients with PCOS resistant to medical therapy, 35 patients with unexplained infertility, and 35 healthy fertile individuals. Patients with PCOS underwent laparoscopic electrocauterization while those with unexplained infertility underwent diagnostic laparoscopy. Serum levels of anti-dsDNA, anti-histone, and anti-nucleosome antibodies were measured at baseline and 1 month after operation and were compared between groups.
Baseline characteristics were similar between groups. Patients with PCOS had significantly higher levels of anti-dsDNA compared to unexplained infertility (p < 0.001) and control groups (p = 0.001). Anti-histone antibodies were higher in PCOS group compared to control group (p = 0.001). In those patients suffering from PCOS, anti-histone antibody increased significantly 1 month after ovarian electrocauterization (p = 0.017). Similarly, serum levels of anti-nucleosome antibodies increased significantly 1 month after operation (p < 0.001).
Laparoscopic ovarian electrocauterization in patients with PCOS results in increased levels of anti-histone and anti-nucleosome antibodies. Anti-dsDNA, anti-histone, and anti-nucleosome antibodies also increase after diagnostic laparoscopy in those with unexplained infertility. Patients with PCOS have higher levels of anti-dsDNA and anti-histone antibodies compared to those with unexplained infertility and healthy fertile subjects.
... The Androgen Excess Society proposed that PCOS should be diagnosed by the presence of three features: androgen excess (clinical and/or biochemical hyperandrogenism), ovarian dysfunction (oligo-anovulation and/or polycystic ovarian morphology), and exclusion of other androgen excess or ovulatory disorders [2]. Although exact pathophysiological mechanisms are not clear, premature adrenarche, obesity, insulin resistance, type 2 diabetes mellitus, endometrial carcinoma, ovulatory dysfunction, androgen excess, polycystic ovaries, complex genetic trait, cardiovascular disease and metabolic syndrome were associated with PCOS [3][4][5][6]. ...
Aim: The aim of this study is to investigate anti-carbonic anhydrase antibodies (anti-CA I and CA II antibodies) in the sera of women with polycystic ovary syndrome (PCOS). Methods: In this study serum anti-CA I and II antibody levels of age and BMI matching fifty women with PCOS and fifty women without PCOS on day three of menstrual cycle were assessed with an ELISA method previously developed by Hosoda and modified by Alver et al. Results: The mean serum anti-CA I antibody levels were significantly higher in women with PCOS and anti-CA II antibody levels were not significantly different in women with PCOS compared with control subjects. For serum anti-CA I antibody, the absorbance higher than 0.484 (mean + 3SD of control subjects) was taken as positive, Anti-CA I antibody was detected in 13 of 50 patients with PCOS (26%). Considering serum anti-CA II antibody, the absorbance higher than 0.654 (mean + 3SD of control subjects) was taken as positive. Anti-CA II antibody was detected in 2 of 50 patients with PCOS (4%). All patients with positive anti-CA II antibody also had positive anti-CA I antibody. Autoantibodies specifically reactive to CA I were found to be present at a higher frequency than CA II in the serum of subjects with PCOS in the present study. Conclusion: The results may suggest that autoimmune responses against CA I may be involved in the pathogenesis of PCOS.
... Interestingly, the accumulation of platelets at the site of tissue injuries seems to be a powerful tool to stimulate immune activation.15 Alborzi et al.16 evaluated anti-ovarian antibodies (AOA) in Clomiphene-resistant PCOS patients before and after electrocauterization. Although their raw data indicated a trend toward rising AOA levels postprocedurally, normalization of the data based on the kit recommendation did not verify the significant production of AOA after laparoscopic ovarian electrocauterization. ...
Polycystic ovary syndrome (PCOS) has been suggested to be linked with autoimmune processes. Laparoscopic ovarian electrocauterization has the potency to stimulate more autoimmune reactions in PCOS patients. In the present study, we considered anti-nuclear antibodies (ANAs) as the hallmark of autoimmune reactions, and investigated the serum level of these antibodies in 35 patients with PCOS (21-38 years old) pre and one-month after electrocauterization, and in 35 fertile healthy women (25-35 years old) as the control group. Serum levels of ANAs, as well as ANA subtyping, were investigated using the Enzyme-Linked Immunosorbent Assay (ELISA). While 3 out of the 35 patients (8.6%) were positive for ANAs before electrocauterization, none of the controls was positive. The number of ANA-positive cases increased following electrocauterization (3 out of 35 [8.6%] before vs. 10 out of 35 [28.6%] after the procedure). The main ANA subtype in the positive samples was SS-A. The higher ANA level among the PCOS patients suggests association of the disease with autoimmune reactions. Laparoscopic ovarian electrocauterization seems to increase the number of positive-ANA patients.
... In women of childbearing age, most functional ovarian cysts are also derived from follicles, as evidenced by polycystic ovarian syndrome (PCOS) (Brassard et al. 2008). Interestingly, PCOS has been known to be closely associated with not only metabolic syndrome and sex-hormone imbalance but also with autoimmune diseases (Alborzi et al. 2009). Inevitably, multiple studies have used murine models to identify candidate genes or exacerbating factors in follicular cysts (Devin et al. 2007; Chapman et al. 2009). ...
MRL/MpJ (MRL) is a model mouse for autoimmune diseases such as dermatitis, vasculitis, arthritis, and glomerulonephritis. In addition to these immune-associated disorders, we found that older MRL mice develop ovarian cysts originating from the rete ovarii, which is lined by ciliated or nonciliated epithelium and considered remnants of mesonephric tubules. Ovarian cysts, which are reported to have several sources, are associated with female infertility, but information regarding the genetic etiology of ovarian cysts originating from the rete ovarii is rare. In this study, to elucidate the genetic background of development of ovarian cysts, we performed quantitative trait locus (QTL) analysis using 120 microsatellite markers, which cover the whole genome of murine chromosomes, and 213 backcross progenies between female MRL and male C57BL/6N mice. The quantitative trait measured was the circumferences of rete ovarii or ovarian cysts. As a result, suggestive linkages were detected on Chrs 3, 4, 6, and 11, but significant linkages were located on Chr 14 by interval mapping. We thereby designated the 27.5-cM region of Chr 14 "MRL Rete Ovarian Cysts (mroc)." The peak regions of Chrs 4 and 14 in particular showed a close additive interaction (p < 0.00001). From these results we concluded that multiple loci on Chrs 3, 4, 6, 11, and 14 interact to result in development of ovarian cysts in MRL mice.
Context
Polycystic ovarian syndrome (PCOS) is a complex disease with different subtypes and unclear etiology. Among the frequent comorbidities are autoimmune diseases, suggesting that autoantibodies (aAb) may be involved in PCOS pathogenesis.
Objective
As the gonadal axis often is dysregulated, we tested the hypothesis that aAb to the gonadotropin-releasing hormone receptor (GnRH-R) are of diagnostic value in PCOS.
Design
An in vitro assay for quantifying aAb to the GnRH-R (GnRH-R-aAb) was established by using a recombinant fusion protein of full-length human GnRH-R and firefly luciferase. A commercial rabbit antiserum to human GnRH-R was used for standardization. Serum samples of control subjects and different cohorts of European PCOS patients (n = 1051) were analyzed.
Results
The novel GnRH-R-aAb assay was sensitive, and signals were linear on dilution when tested with the commercial GnRH-R antiserum. Natural GnRH-R-aAb were detected in one control (0.25%) and two PCOS samples (0.31%), and 12 samples were slightly above the threshold of positivity. The identification of samples with positive GnRH-R-aAb was reproducible and the signals showed no matrix interferences.
Conclusion
Natural GnRH-R-aAb are present in a very small fraction of adult control and PCOS subjects of European decent. Our results do not support the hypothesis that the GnRH-R constitutes a relevant autoantigen in PCOS.
Sperm of humans, non-human primates, and other mammalian subjects is considered to be antigenic. The effect of changes in autoimmunity on reproductive cells such as spermatozoa and oocytes play a critical but indistinct role in fertility. Antisperm antibodies (ASAs) are invariably present in both females and males. However, the degree of ASA occurrence may vary according to individual and gender. Although the extent of infertility due to ASAs alone is yet to be determined, it has been found in almost 9–12% of patients who are infertile due to different causes. Postcoital presence of spermatozoa in the reproductive tract of women is not a contributory factor in ASA generation. However,ASA generation may be induced by trauma to the vaginal mucosa, or by anal or oral sex resulting in the deposition of sperm inside the digestive tract. It is strongly believed that, in humans and other species, at least some antibodies may bind to sperm antigens, causing infertility. This form of infertility is termed as immunological infertility, which may be accompanied by impairment of fertility, even in individuals with normozoospermia. Researchers target ASAs for two major reasons: (i) to elucidate the association between ASAs and infertility, the reason ASAs causes infertility, and the mechanism underlying ASA-mediated infertility;and (ii) to assess the potential of ASAs as a contraceptive in humans in case ASAs influences infertility. Therefore, this review explores the potential application of ASAs in the development of anti-spermatozoa vaccines for contraceptive purposes. The usefulness of ASAs for diagnosing obstructive azoospermia, salpingitis, and oligoasthenoteratozoospermia has been reviewed extensively. Important patents pertaining to potential candidates for spermatozoa-derived vaccines that may be utilized as contraceptives are discussed in depth. Antifertility vaccines, as well as treatments for ASA-related infertility, are also highlighted. This review will address many unresolved issues regarding mechanisms involvingASAs in the diagnosis, as well as prognoses, of male infertility. More documented scientific reports are cited to support the mechanisms underlying the potential role of ASA in infertility. The usefulness of sperm antigens or ASAs (recombinant) in human and wild or captive animal contraceptive vaccines has been revealed through research but is yet to be validated via clinical testing.
Human gonadal and adrenal tissue is a frequent target for an autoimmune attack in various circumstances leading to ovarian, testicular, and adrenal dysfunction. From numerous gonadal and adrenal components serving as possible antigens, the steroid-producing cells are the most frequent targets for antibody production. The steroid cell antibodies (SCA) can be detected in high numbers (90%) of patients with premature ovarian failure (POF) and Addison disease, and in more than 30% of patients with autoimmune polyglandular syndrome type II (APS-II). Several different target antigens are involved in ovarian autoimmunity, and, among all the cell types that are under immune target, the oocyte is the most immunodominant of all. Antiovarian (AOA), antioocyte, anticorpus luteum, as well as antizona pellucida antibodies can be detected with various prevalence. From these, evaluation of AOA can be effective as a prognostic factor in management of infertile patients. Antisperm antibodies directed to the basal membrane of the seminiferous tubules are the most frequent finding in sera of patients with autoimmune orchitis. Among adrenal cortex antigens, 21-hydroxylase has been found as the main immunologic target for antibody production, and 17β-hydroxylase and side-chain-cleavage enzyme (SCC) were identified as additional antigens. High sensitivity and specificity of 21-hydroxylase antibodies, together with good predictive value, make the measurement of 21-hydroxylase antibodies the first step in immune assessment of patients with Addison disease and individuals at risk for adrenal autoimmunity.
In this report, we propose an intervention capable of improving IVF outcomes in subfertile women with poor ovarian response. This intervention derives from anecdotal data and observations in our daily practice, but most importantly from trials on experimental models and subfertile women with Polycystic Ovarian Syndrome (PCOS). Our hypothesis suggests that transvaginal induction of trauma to the ovary in the cycle preceding IVF should benefit poor ovarian responders and their lowered pregnancy rates by increasing –at least- the number of retrieved oocytes during oocyte retrieval. Up-to-the minute data show that, via this means, there is a unique response of the ovarian surface epithelium and stroma to the induced trauma. The potential pathways of this beneficial response involve an improvement of the raised gonadotrophins to act either through the mechanical reduction of the size of the ovary or through alterations of the hormonal profile by lowering LH, inhibin and local androgen concentrations through hypothalamic-pituitary axis feedbacks, the induction of increased blood flow to the ovaries, a differentiated local immune reaction and a non-elucidated as yet role of reactive oxygen species. In this report, we also describe the technique and the associated possible negative points while we try to point out the needed research steps to ensure its efficiency before it enters daily clinical practice.
Objective
To evaluate levels of the circulating antisperm antibody (ASA) in infertile women with polycystic ovary syndrome (PCOS).
Methods
Forty-six infertile women with PCOS were enrolled into this study. The serum was screened by the indirect immunobead test for ASA type IgG and IgA according to the WHO laboratory manual.
Results
Of the 46 patients assessed for ASA-IgG, 3 cases had immunobead binding which were 20%, 27% and 35%, respectively, and the sub-positive rate was 6.5%. No case had the clinical positive level according to the WHO criteria (50% or more of the motile sperm with immunobead binding). ASA-IgA was not detected in all cases.
Conclusions
The circulating ASA is not associated with the pathogenesis of infertile women with PCOS.
Background:
The introduction of laparoscopic ovarian drilling (LOD) by Gjönnaess in 1984 as a substitute for ovarian wedge resection created opportunities for extensive research given its worldwide application for ovulation induction in women with polycystic ovary syndrome (PCOS).
Purpose:
To critically evaluate and summarize the current body of literature regarding the role of LOD for the management of PCOS entailing its different preoperative, operative and postoperative aspects. In addition, long-term efficacy, cost-effectiveness, patient preference and health-related quality of life issues will be evaluated together with other available alternatives of ovulation induction treatments.
Methods:
A PubMed search was conducted looking for the different trials, reviews and various guidelines relating to the role of LOD in the management of PCOS.
Results:
LOD whether unilateral or bilateral is a beneficial second-line treatment in infertile women with clomiphene citrate (CC)-resistant PCOS. It is as effective as gonadotrophin treatment but without the risk of multiple pregnancy or ovarian hyperstimulation and does not require intensive monitoring. Increased responsiveness of the ovary to CC especially in patients who remain anovulatory following LOD is another advantage. Recent evidence suggests that relatively novel oral methods of ovulation induction, e.g. CC plus metformin, CC plus tamoxifen, rosiglitazone plus CC and aromatase inhibitors represent a successful alternative to LOD in CC-resistant PCOS. Meanwhile current evidence does not support LOD as a first-line approach in PCOS-related anovulation or before IVF.
Conclusion:
LOD is currently recommended as a successful and economical second-line treatment for ovulation induction in women with CC-resistant PCOS.
The human ovary is commonly the target of an autoimmune attack leading to the ovarian dysfunction which can be manifested as premature ovarian failure (POF), polycystic ovary syndrome (PCOS), unexplained infertility as well as endometriosis. In case of POF, the evidence for an autoimmune etiology is based on the presence of lymphocytic oophoritis, autoantibodies to ovarian antigens and association with other autoimmune disorders, which was clearly documented in many studies. The search for antiovarian antibodies has been undertaken in numerous studies, especially in patients with POF, however their results are still conflicting particularly due to difference in laboratory methods as well as many ovarian components being potential antigens. On the other side the autoimmune etiology of PCOS is still debated and was documented in some cases. Association of PCOS with non-organ specific autoimmune disorders is controversial; however association with autoimmune thyroid disease was well demonstrated in some studies.
Laparoscopic ovarian drilling (LOD) is an alternative to ovulation induction with gonadotropins for polycystic ovarian syndrome (PCOS) patients unresponsive to clomiphene. It is quick and easy to perform, although the number of punctures and energy doses has not been standardized. The mechanism of LOD is unclear, but it is likely mediated by a reduction in intraovarian androgen production. Serum luteinizing hormone and testosterone levels are rapidly normalized, and these changes are sustained over long-term follow-up. Studies have shown that ovulation and pregnancy rates are comparable between ovulation induction with gonadotropins and LOD, but LOD avoids the risks of multiple pregnancy and ovarian hyperstimulation syndrome. LOD is also more cost effective and better tolerated than gonadotropin therapy. Concerns regarding clinically significant adhesion formation and premature ovarian failure are not supported by the available data. Transvaginal hydrolaparoscopy and ultrasound guidance are less invasive techniques for performing ovarian drilling and may encourage LOD earlier in the course of treatment for PCOS.
BACKGROUND: Currently, there is an uncertainty about the impact of laparoscopic ovarian drilling (LOD) on the natural history
of polycystic ovarian syndrome (PCOS). This longitudinal follow-up study was undertaken to investigate the long-term effects
of LOD. METHODS: The study included 116 anovulatory PCOS women who underwent LOD between 1991 and 1999 (study group) and 34
anovulatory PCOS women diagnosed during the same period but who had not undergone LOD (comparison group). The hospital records
were reviewed and questionnaires were sent to all the women. In addition, most women attended a follow-up interview. Clinical
data recorded at different intervals of follow-up (short-term, <1 year; medium-term, 1–3 years; and long-term, 4–9 years)
included: the menstrual pattern, symptoms relating to hyperandrogenaemia and reproductive history. RESULTS: The proportion
of women with regular menstrual cycles increased significantly [relative risk (RR) = 1.6, 95% confidence interval (CI) = 1.4–1.9,
P < 0.05] from 8% before LOD to 67% post-operatively. The proportion dropped to 37% (RR = 2.6, 95% CI = 1.8–3.8, P < 0.01) at medium-term follow-up and then increased again to 55% (RR = 2.2, 95% CI = 1.7–2.8, P < 0.01) at long-term follow-up. After LOD, 54/110 women (49%) conceived spontaneously during the first year and 42 (38%)
during medium- and long-term follow-up. Among women with hirsutism (n = 43) and acne (n = 25), 10 (23%) and 10 (40%) respectively experienced long-term improvement after LOD. CONCLUSION: LOD produces long-term
improvement in menstrual regularity and reproductive performance in about one-third of cases. A modest and sustained improvement
in acne and hirsutism can be expected in ~40 and ~25% of patients respectively.
Autoimmunity may be involved in idiopathic premature ovarian failure (POF). However, the frequency, physiopathology and potential reversibility of autoimmune oophoritis needs clarification, Using an ELISA against whole tissue homogenate as antigen, from human ovaries at different ages, positive circulating ovarian antibodies (AOA) were found in 59% of patients with primitive idiopathic POF (27/46); 20/27 were positive for IgG isotype, 9/27 for IgM and 8/27 for IgA, Specificity of AOA was examined (i) by comparison to different control groups; mean values of the three subclasses of immunoglobins were significantly higher in POF women than in normally cycling fertile young women (n = 23) and fertile young men (It 17), in untreated Grave's disease (n = 35) or in women with positive antinuclear factor (n = 25); and (ii) by assessing possible cross-reaction; only six out of the 27 positive sera reacted with other tissues (thyroid, pancreas, adrenal), including four clinical polyendocrinopathies. Significance of AOA was explored (i) by comparison with postmenopausal women (n = 40) and older women (n = 15), who did not have enhanced ratios of AOA, thereby excluding a potential role of high FSH values; (ii) by analysing the factors time and surgery; no relation could be found either with the duration of amenorrhoea (6 months to 21 years) or with the history of an ovarian biopsy (12/47) in the absence of any associated pelvic surgery; and (iii) by screening for other immunological factors; familial or personal autoimmune disease (8/46), HLA DR3 (10/42), HLA DR4 (11/42), associated autoantibodies (thyroperoxidase, adrenal, beta islets, parathyroid, DNA, smooth muscles) (12/42), If one positive AOA isotype was present, a second immunological factor was found in 45% of cases, Spontaneous pregnancies during oestrogen therapy occurred in four cases, including three women with positive AOA, Circulating AOA detected by an ELISA may represent a practical and suitable marker for diagnosis of POF, Its use for prognosis and rational treatment needs further evaluation.
Anti-ovary antibodies (AOA) have been detected in serum samples of women undergoing in vitro fertilization (IVF). High concentrations of these antibodies have been found in women who have had several IVF attempts and they appear to correlate with reduced chances of pregnancy. In this paper, AOA were assayed sequentially in a series of 140 IVF candidates to investigate the respective roles of hormonal stimulation and follicular puncture in inducing the autoimmune response. Serum was obtained 8 days after the beginning of ovarian human menopausal gonadotrophin (hMG) stimulation, then 15 days after follicular puncture. Significantly higher concentrations of IgG (P < 0.0001) AOA were observed in the second series of samples than in the first, suggesting that ovarian trauma and not hormonal stimulation is responsible for triggering antibody production. In the whole group, there was a negative correlation between IgM levels after puncture and oocyte numbers (P < 0.05). Among 'immune-responder' women, the concentrations of IgA AOA (P = 0.01) in the first sample, and of IgG (P = 0.01) or IgA AOA (P < 0.05) in the second, correlated with fewer oocytes after stimulation. There was no variation in the mean concentrations of AOA in women who achieved pregnancy.
Twenty-one nulliparous oligomenorrheic women with polycystic ovaries, complaining of infertility (mean duration 6 years) refractory to medical treatment, underwent laparoscopic ovarian diathermy. Eleven had adhesions and/or endometriosis. Regular ovulatory cycles ensued in 17 women (81%). In 9 responders there was a transient rise in mean follicle-stimulating hormone from 5.0 +/- 0.4 (standard error of the mean [SEM]) to 6.7 +/- 0.5 mIU/mL on postoperative day 1 and a fall in testosterone from 2.6 +/- 0.2 to 1.9 +/- 0.2 nmol/L by day 8. Luteinizing hormone fell from 19 +/- 1.2 to 10.4 +/- 1.2 mIU/mL by the follicular phase of the next cycle. Eleven women have conceived 13 pregnancies; 3 miscarried, 7 were delivered at term and 3 are ongoing. Ovarian diathermy is a useful option in women with polycystic ovaries complaining of refractory anovulatory infertility.
Autoimmunity may be involved in idiopathic premature ovarian failure (POF). However, the frequency, physiopathology and potential reversibility of autoimmune oophoritis needs clarification. Using an ELISA against whole tissue homogenate as antigen, from human ovaries at different ages, positive circulating ovarian antibodies (AOA) were found in 59% of patients with primitive idiopathic POF (27/46); 20/27 were positive for IgG isotype, 9/27 for IgM and 8/27 for IgA. Specificity of AOA was examined (i) by comparison to different control groups; mean values of the three subclasses of immunoglobins were significantly higher in POF women than in normally cycling fertile young women (n = 23) and fertile young men (n = 17), in untreated Grave's disease (n = 35) or in women with positive antinuclear factor (n = 25); and (ii) by assessing possible cross-reaction; only six out of the 27 positive sera reacted with other tissues (thyroid, pancreas, adrenal), including four clinical polyendocrinopathies. Significance of AOA was explored (i) by comparison with postmenopausal women (n = 40) and older women (n = 15), who did not have enhanced ratios of AOA, thereby excluding a potential role of high FSH values; (ii) by analysing the factors time and surgery; no relation could be found either with the duration of amenorrhoea (6 months to 21 years) or with the history of an ovarian biopsy (12/47) in the absence of any associated pelvic surgery; and (iii) by screening for other immunological factors; familial or personal autoimmune disease (8/46), HLA DR3 (10/42), HLA DR4 (11/42), associated autoantibodies (thyroperoxidase, adrenal, beta islets, parathyroid, DNA, smooth muscles) (12/42). If one positive AOA isotype was present, a second immunological factor was found in 45% of cases. Spontaneous pregnancies during oestrogen therapy occurred in four cases, including three women with positive AOA. Circulating AOA detected by an ELISA may represent a practical and suitable marker for diagnosis of POF. Its use for prognosis and rational treatment needs further evaluation.
The involvement of autoimmune mechanisms in premature ovarian failure has been put forward by numerous investigators. In various other ovarian pathologies, such as idiopathic infertility, polycystic ovary syndrome, or endometriosis, similar mechanisms have been suggested. However, the exact role of autoimmunity in the pathophysiology of these diseases still remains controversial. The diagnosis of autoimmune ovarian disease relies on several clinical, biological and histological findings, but special interest has been focused on antiovarian autoantibodies. The search for these antibodies has been undertaken by several authors and yielded somewhat conflicting results which might be conditioned by methodological differences and by the multiplicity of potential immune targets. These targets, which comprise various steroidogenic enzymes, gonadotrophins and their receptors, the corpus luteum, zona pellucida and oocyte, are reviewed. Further investigation of these targets is required to improve the diagnostic tools that will lead to a precocious and reliable diagnosis of autoimmune ovarian disease, an appropriate clinical surveillance as well as the selection of patients who may benefit from immune-modulating therapy and possibly recover ovarian function and fertility.
Although laparoscopic ovarian drilling (LOD) has been widely used to induce ovulation in women with polycystic ovarian syndrome (PCOS), predicting the clinical response to this treatment remains to be elucidated further. This study was carried out to identify factors that may help to predict the outcome of LOD.
This retrospective study included 200 patients with anovulatory infertility due to PCOS who underwent LOD between 1990 and 2002. The influence of the various patients' pre-operative characteristics on the ovulation and pregnancy rates after LOD was evaluated. In addition, women were divided into two or three categories according to the severity of each of the various clinical and biochemical parameters of PCOS. The success rates were compared between the categories of each factor using contingency table analyses. Multiple logistic regression analysis was used to identify independent predictors of success of LOD.
Women with body mass index (BMI) > or = 35 kg/m2, serum testosterone concentration > or = 4.5 nmol/l, free androgen index (FAI) > or = 15 and/or with duration of infertility > 3 years seem to be poor responders to LOD. In LOD responders, serum LH levels > 10 IU/l appeared to be associated with higher pregnancy rates.
Marked obesity, marked hyperandrogenism and/or long duration of infertility in women with PCOS seem to predict resistance to LOD. High LH levels in LOD responders appear to predict higher probability of pregnancy.
The aim of the study was to analyze the use of endoscopic procedures in the group of infertile patients.
The study material consisted of 636 patients, aged 20-41. They all had endoscopic procedures performed (laparoscopy and/or hysteroscopy) due to infertility, and were qualified for the procedure after a gynecological examination and ultrasound scan. The study group was divided into subgroups of primary and secondary sterility and endoscopic procedures were then analyzed.
A total of 724 endoscopic procedures were performed on 636 patients. Eighty eight women had both hysteroscopy and laparoscopy performed, 476 had only laparoscopy, while 72--only hysteroscopy. Women diagnosed due to primary sterility more often had no visible abnormalities in the pelvic region (30%) and patent oviducts than those with secondary sterility. The remaining 70% more often had ovaries typical for polycystic ovarian syndrome and endometriosis. However, periadnexal adhesions and tubal impotency were more common in the group of secondary sterility. As to hysteroscopy, women with primary sterility more often had congenital uterine malformations, while submucosal myomas and intrauterine adhesions were less common in that group. All the surgical procedures performed during laparoscopies were analyzed. Tubal patency assessment and ovarian drilling were significantly more often performed in the subgroup of primary sterility. All intrauterine pathologies were treated during hysteroscopy.
Laparoscopy and hysteroscopy play an important role as both diagnostic and therapeutic tools in the infertility treatment centers.
Objective To determine whether the microtrauma induced by repeated puncture of ovarian follicles could result in the production of autoantibodies in women submitted to in vitro fertilization (IVF). Design Antiovarian antibodies were assayed in serum samples obtained from women engaged in IVF and in serum samples from healthy controls. Setting Blood samples were obtained after oocyte collection in the local hospital’s IVF unit. Patients One hundred ten women undergoing IVF entered the study. Oocyte division, numbers of embryos, and pregnancy were recorded for each woman. Control samples were from 40 individuals with no sign of autoimmune disorder. Interventions Antiovarian antibodies were assayed in indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) using human ovary as antigen. Specific immunoglobulin (Ig)G, IgA, and IgM were tested separately in an ELISA. Main outcome measure Antiovarian antibody levels were compared between patients and controls and correlated with the subsequent results of IVF. Results Significantly higher levels of IgG, IgA, and IgM antiovarian antibodies were observed in the group of IVF women ( P P P Conclusions These data suggest that ovarian trauma may lead to the production of autoantibodies.
In the field of surgery the deveiopment of operative laparoscopy has been one of the most important steps forward over the past fifteen years. This technique has become the surgical treatment of choice for a number of indications in gynaecology. The advantages of laparoscopy as compared with laparotomy are weil known, and assessment of the risk of complications is essential. A multicentric study was carried out in seven top French centres for laparoscopic gynaecological surgery. This series runs over a period of nine years and covers 29,966 diagnostic and operative laparoscopies. The risk of complications has been assessed according to the compiexity of the laparoscopic procedure in question. The means of diagnosis and treatment of the complications have been analysed together with the importance of the surgeon’s degree of experience. The mortality rate is 3.33 per hundred thousand laparoscopies. The overail complication rate is 4.64 per thousand laparoscopies (139 cases). The rate of complications requiring laparotomy is 3.20 per thousand (96 cases). The complication rate is significantly correlated with the complexity of the laparoscopic procedure (p = 0.0001). One out of three complications (34.1 % ; 43 cases) occurred while setting up for laparoscopy, and one out of four complications (28.6 %) were not diagnosed during the operation. As new indications for laparoscopic surgery in gynaecology have appeared, there has been a parallel and statistically significant increase in the rate of urological complications (p = 0.001). Increased experience of the surgeons has had three consequences : a statistically significant drop in the number of bowel injuries (p = 0.0003), a drop in the rate of complications requiring laparotomy for those laparoscopic surgical procedures which are weil-defined (p = 0.01) and a change in the way complications are treated, with a significant increase in the proportion of incidents treated by laparoscopy (p = 0.0001). Laparoscopic surgery is a reliable technique. The risk of complications exists whatever the indication for laparoscopy. None of the phases in the operation must be neglected. The risk of accidents being overlooked means that the methods for postoperative follow-up must be adapted, bearing in mind the shorter hospital stay. The part played by the surgeon’s experience raises the major probiern of practitioner training.
Objectives. – To assess anti-ovarian antibodies (AOA) in serum samples at various times of in vitro fertilization (IVF) attempts to determine whether ovarian stimulation could result in the production of such autoantibodies in women.Patients and methods. – Prospective study on 134 patients and 138 IVF cycles using a classical long protocol. For each attempt, four serum samples were obtained, respectively, at the onset of downrelation (S1), end of downregulation (S13), after 7 days of follicular stimulation (S21) and the day of follicular puncture (SP). Five hundred and fifty two samples were tested with an enzyme-linked immunosorbent assay for three isotypes (IgG, IgA, IgM) of AOA.Results. – In the whole group, mean concentrations of AOA for each isotype were compared group by group: S1–S13, S1–S21, S1–SP, S13–S21, S13–SP, S21–SP. Not any significant difference was observed whatever the isotype considered.Discussion and conclusion. – This study shows the absence of influence of endogenous or exogenous ovarian stimulation by gonadotropins on anti-ovarian autoimmunity.
In previous papers, we referred to studies of the influence of anti-ovarian autoantibodies on menstrual cycle disorders in adolescent girls. We examined autoantibodies against ooplasma, zona pellucida, membrana granu-losa, theca folliculi interna, and lutein cells. In infertile women in the IVF/ET program, we studied the positivity of antiovarian antibodies and cytokines, namely, TNF- and IL-1β, in follicular fluid correlated with the following sub-groups, characterized by the outcome of in vitro fertilization, as follows: G, pregnant; F, fertilized; N, nonfertilized; and O, no oocyte gained. The presence of autoantibodies corresponds to the success or failure of the IVF/ET program. Our results support the hypothesis that antiovarian autoantibodies play an important role in both the endocrine and the reproductive function of the human ovary and that it can influence them negatively.
To determine whether the microtrauma induced by repeated puncture of ovarian follicles could result in the production of autoantibodies in women submitted to in vitro fertilization (IVF).
Antiovarian antibodies were assayed in serum samples obtained from women engaged in IVF and in serum samples from healthy controls.
Blood samples were obtained after oocyte collection in the local hospital's IVF unit.
One hundred ten women undergoing IVF entered the study. Oocyte division, numbers of embryos, and pregnancy were recorded for each woman. Control samples were from 40 individuals with no sign of autoimmune disorder.
Antiovarian antibodies were assayed in indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) using human ovary as antigen. Specific immunoglobulin (Ig)G, IgA, and IgM were tested separately in an ELISA.
Antiovarian antibody levels were compared between patients and controls and correlated with the subsequent results of IVF.
Significantly higher levels of IgG, IgA, and IgM antiovarian antibodies were observed in the group of IVF women (P less than 0.001). IgM antiovarian antibodies correlated with a lower number of embryos (P less than 0.001) and IVF failure (P less than 0.05).
These data suggest that ovarian trauma may lead to the production of autoantibodies.
The presence of antiovarian antibodies in sera of women with premature ovarian failure was determined by an indirect fluorescent antibody assay using human ovarian tissue. Of 27 patients, 14 had positive ovarian fluorescence, compared with zero of 24 normal cycling controls (P less than .001) and one of 22 postmenopausal controls (P less than .01). In patients with autoimmune diseases, five of 17 demonstrated positive fluorescence compared with zero of 24 premenopausal controls (P less than .01). Immunoperoxidase staining revealed antigen concentrated at the granulosa cells and oocyte in nine of the 14 ovarian failure cases. The finding that a significant proportion of patients with premature ovarian failure have circulating antiovarian antibodies confirms previous studies, but localization of peroxidase staining to granulosa cells and/or oocytes represents a new finding in this study.
Sixty-two women with the polycystic ovarian syndrome were treated by systematic electrocautery of the ovarian capsule performed by laparoscopy. Ovulation occurred within 3 months in 92%. Regular menstrual cycles were established in 51 patients (86%) and plasma progesterone levels suggested that these were ovulatory. Seven of nine women who had been resistant to treatment with clomiphene, 150 mg daily, and human chorionic gonadotropin, 6000 to 9000 IU, ovulated after electrocauterization. The remaining two women responded to stimulation with clomiphene. Pregnancy occurred in 24 of 35 subjects who were involuntarily infertile (69%), with the pregnancy rate increasing to 80% with the inclusion of the women sensitive to clomiphene. These findings support the theory that ovulation is triggered by local factors within the ovary itself.
To compare the presence in levels of antiovarian antibodies (AOAb) in the pre- and postovulatory stage from serum of infertile patients undergoing intrauterine insemination (IUI) or in vitro fertilization (IVF) with outcome of the procedures.
Serum from 36 women undergoing IUI, 36 women undergoing IVF and 25 fertile, healthy controls were assayed for the presence of AOAb by a commercially available ELISA kit. AOAb was positive in 59.7% of infertile women, while none of the fertile controls were positive for AOAb. The levels of these antibodies increased as the patient age and the number of treatment attempts increased. Though the presence of AOAb did not affect oocyte recovery rate, it resulted in decreased fertilization rate, cleavage rate, and pregnancy rate in infertile women.
Our studies suggest that AOAb may be a cause of infertility and presence of these antibodies could have adverse effects on the outcome of assisted reproductive techniques.
The use of laparoscopic techniques for the treatment of polycystic ovarian syndrome (PCOS) has included many different approaches in the 1980s and 90s. Broadly similiar results have been obtained using biopsy, cauterization, multi-electrocoagulation and laser surgery; i.e. > 50% ovulation and a mean pregnancy rate of 50%. Evaluation of the data is complicated by the lack of uniformity in these clinical studies and the variation in diagnostic criteria. None of the studies included a treatment-independent control group. Endocrine changes following laparoscopy have been identified in many studies, but the mode of action of these treatments remains a mystery. In conclusion, laparoscopic techniques have the advantage over surgical wedge resection of cost saving and a lower risk of post-operative adhesions. For clomiphene resistant patients, laparoscopic techniques have many advantages over gonadotrophin therapy including serial repetitive ovulation events, no increased risk of ovarian hyperstimulation or multiple pregnancies and a lower incidence of spontaneous abortion, but these procedures must not be considered as the first line treatment for the anovulatory patient with PCOS, for whom clomiphene citrate remains the first choice mode of therapy.
To compare the effects of microlaparoscopy and decreased CO2 exposure on peritoneal microcirculation and potential adhesion formation after ovarian surgery with those of conventional operative laparoscopy.
Prospective, randomized study (Canadian Task Force classification I).
Teaching hospital.
Eighteen women with polycystic ovary disease.
Microlaparoscopic or laparoscopic ovarian coagulation of the ovaries.
Approximately 10 to 12 coagulation points were applied to each ovary. Two to 3 weeks after the initial surgery second-look microlaparoscopy was performed to determine the extent of adhesions in both groups. The frequency of adhesion formation and changes in glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were studied in homogenized peritoneal tissues obtained during surgery in each group.
Clinical profiles were similar between groups. Mean exposure, amount, and pressure of CO2 were significantly less in the microlaparoscopy group (p <0.05). The laparoscopy group had significantly more adhesions than the microlaproscopy group (24% vs 48%, p <0.05). The GSH-Px, SOD, CAT, and GSH levels were significantly lower in the laparoscopy group (0. 425 micromol, 1.2 ng, 37.55 micromol, and 0.9 nmol vs 0.755 micromol, 2.l ng, 625 micromol, and 2.6 nmol, respectively).
Reduced exposure to and amount of CO2 during microlaparoscopy may result in decreased adhesion formation compared with conventional laparoscopy. This effect may possibly be due to lack of or minimal adverse effects on peritoneal microcirculation and cell-protective systems, which are proposed mechanisms for adhesion formation and closely related to peritoneal injury. In addition, microlaparoscopy may be a cost-effective alternative to conventional laparoscopy. (J Am Assoc Gynecol Laparosc 6(2):159-163, 1999)
In previous papers, we referred to studies of the influence of antiovarian autoantibodies on menstrual cycle disorders in adolescent girls. We examined autoantibodies against ooplasma, zona pellucida, membrana granulosa, theca folliculi interna, and lutein cells. In infertile women in the IVF/ET program, we studied the positivity of antiovarian antibodies and cytokines, namely, TNF-alpha and IL-1 beta, in follicular fluid correlated with the following subgroups, characterized by the outcome of in vitro fertilization, as follows: G, pregnant; F, fertilized; N, nonfertilized; and O, no oocyte gained. The presence of autoantibodies corresponds to the success or failure of the IVF/ET program. Our results support the hypothesis that antiovarian autoantibodies play an important role in both the endocrine and the reproductive function of the human ovary and that it can influence them negatively.
To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size.
Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared.
Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences.
Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.
In the field of surgery the development of operative laparoscopy has been one of the most important steps forward over the past fifteen years. This technique has become the surgical treatment of choice for a number of indications in gynaecology. The advantages of laparoscopy as compared with laparotomy are weil known, and assessment of the risk of complications is essential. A multicentric study was carried out in seven top French centres for laparoscopic gynaecological surgery. This series runs over a period of nine years and covers 29,966 diagnostic and operative laparoscopies. The risk of complications has been assessed according to the complexity of the laparoscopic procedure in question. The means of diagnosis and treatment of the complications have been analysed together with the importance of the surgeon's degree of experience. The mortality rate is 3.33 per hundred thousand laparoscopies. The overall complication rate is 4.64 per thousand laparoscopies (139 cases). The rate of complications requiring laparotomy is 3.20 per thousand (96 cases). The complication rate is significantly correlated with the complexity of the laparoscopic procedure (p = 0.0001). One out of three complications (34.1%; 43 cases) occurred while setting up for laparoscopy, and one out of four complications (28.6%) were not diagnosed during the operation. As new indications for laparoscopic surgery in gynaecology have appeared, there has been a parallel and statistically significant increase in the rate of urological complications (p = 0.001). Increased experience of the surgeons has had three consequences: a statistically significant drop in the number of bowel injuries (p = 0.0003), a drop in the rate of complications requiring laparotomy for those laparoscopic surgical procedures which are weil-defined (p = 0.01) and a change in the way complications are treated, with a significant increase in the proportion of incidents treated by laparoscopy (p = 0.0001). Laparoscopic surgery is a reliable technique. The risk of complications exists whatever the indication for laparoscopy. None of the phases in the operation must be neglected. The risk of accidents being overlooked means that the methods for postoperative follow-up must be adapted, bearing in mind the shorter hospital stay. The part played by the surgeon's experience raises the major problem of practitioner training.
Currently, there is an uncertainty about the impact of laparoscopic ovarian drilling (LOD) on the natural history of polycystic ovarian syndrome (PCOS). This longitudinal follow-up study was undertaken to investigate the long-term effects of LOD.
The study included 116 anovulatory PCOS women who underwent LOD between 1991 and 1999 (study group) and 34 anovulatory PCOS women diagnosed during the same period but who had not undergone LOD (comparison group). The hospital records were reviewed and questionnaires were sent to all the women. In addition, most women attended a follow-up interview. Clinical data recorded at different intervals of follow-up (short-term, <1 year; medium-term, 1-3 years; and long-term, 4-9 years) included: the menstrual pattern, symptoms relating to hyperandrogenaemia and reproductive history.
The proportion of women with regular menstrual cycles increased significantly [relative risk (RR) = 1.6, 95% confidence interval (CI) = 1.4-1.9, P < 0.05] from 8% before LOD to 67% post-operatively. The proportion dropped to 37% (RR = 2.6, 95% CI = 1.8-3.8, P < 0.01) at medium-term follow-up and then increased again to 55% (RR = 2.2, 95% CI = 1.7-2.8, P < 0.01) at long-term follow-up. After LOD, 54/110 women (49%) conceived spontaneously during the first year and 42 (38%) during medium- and long-term follow-up. Among women with hirsutism (n = 43) and acne (n = 25), 10 (23%) and 10 (40%) respectively experienced long-term improvement after LOD.
LOD produces long-term improvement in menstrual regularity and reproductive performance in about one-third of cases. A modest and sustained improvement in acne and hirsutism can be expected in approximately 40 and approximately 25% of patients respectively.
To assess anti-ovarian antibodies (AOA) in serum samples at various times of in vitro fertilization (IVF) attempts to determine whether ovarian stimulation could result in the production of such autoantibodies in women.
Prospective study on 134 patients and 138 IVF cycles using a classical long protocol. For each attempt, four serum samples were obtained, respectively, at the onset of downrelation (S1), end of downregulation (S13), after 7 days of follicular stimulation (S21) and the day of follicular puncture (SP). Five hundred and fifty two samples were tested with an enzyme-linked immunosorbent assay for three isotypes (IgG, IgA, IgM) of AOA.
In the whole group, mean concentrations of AOA for each isotype were compared group by group: S1-S13, S1-S21, S1-SP, S13-S21, S13-SP, S21-SP. Not any significant difference was observed whatever the isotype considered.
This study shows the absence of influence of endogenous or exogenous ovarian stimulation by gonadotropins on anti-ovarian autoimmunity.
To assess changes in serum hormone levels and ovarian stromal blood flow after laparoscopic ovarian drilling (LOD) in young adult women with polycystic ovary syndrome (PCOS).
Prospective, nonrandomized study (Canadian Task Force classification II-1).
Tertiary care, major teaching hospitals.
Anovulatory young women with PCOS who were resistant to clomiphene citrate.
Laparoscopic ovarian drilling.
To evaluate the endocrinological effects of LOD, serum leptin, insulin-like growth factor-1, estrone (E1), and estradiol were measured before and after ovarian drilling in the early follicular phase. Three-dimensional transabdominal power Doppler examinations were performed to determine the effects of LOD. Serum leptin was correlated with body mass index (BMI) before LOD. Levels of BMI, fasting blood sugar, and leptin were higher and LH, LH/FSH, and the sugar/insulin ratio were lower in the obese group. There were significant decreases in the free androgen index, and total testosterone, luteinizing hormone (LH), and LH/follicle-stimulating hormone (FSH) levels, and a significant increase in sex hormonebinding globulin (SHBG) concentration in the 3 months after the operation. The vascularization index and vascularization flow index of the intraovarian stroma significantly decreased after treatment. Reversed correlations between leptin and LH, LH/FSH, E1, thyroid-stimulating hormone, and SHBG were noted 3 months after the operation compared with levels obtained before the operation.
Treatment of young adult women with PCOS using LOD did not influence leptin levels but changed the ovarian stromal blood flow dynamics during short-term follow-up. The surgical procedure may be beneficial both to endocrine profiles and to intraovarian stromal flow in patients with PCOS.
To determine whether the ovarian trauma consequent to the laparoscopic removal of a cyst could result in the development of a humoral immunity, antiovarian antibodies were assayed in serum samples obtained from 40 women before and after cystectomy.