Hakan Cakmak

Yale University, New Haven, CT, United States

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Publications (39)94.99 Total impact

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    ABSTRACT: Asherman's Syndrome is characterized by intrauterine adhesions or fibrosis resulting as a consequence of damage to the basal layer of endometrium and is associated with infertility due to loss of normal endometrium. We have previously shown that bone marrow derived stem cells (BMDSCs) engraft the endometrium in mice and humans and Ischemia/reperfusion injury of uterus promoted BMDSCs migration to the endometrium; however, the role of BMDSCs in Asherman's syndrome has not been characterized. Here a murine model of Asherman's syndrome was created by traumatizing the uterus. We evaluate stem cell recruitment and pregnancy after BMDSCs transplantation in a model of Asherman's syndrome. In the Asheman's syndrome model, after BMDSC transplant, the Y chromosome bearing CD45-cells represented less than 0.1% of total endometrial cells. Twice the number of Y+CD45- cells was identified in the damaged uterus compared to the uninjured controls. There was no significant difference between the damaged and undamaged uterine horns in mice that received injury to a single horn. In the BMDSC transplant group, 9 of the 10 mice conceived, while only 3 of 10 in the non-transplanted group conceived (Chi-Square p = 0.0225); all mice in an uninjured control group conceived. The time to conception and mean litter size were not different between groups. Taken together, BMDSCs are recruited to endometrium in response to injury. Fertility improves after BMDSC transplant in Asherman's Syndrome mice, demonstrating a functional role for these cells in uterine repair. BMDSC transplantation is a potential novel treatment for Asherman's Syndrome and may also be useful to prevent Asherman's syndrome after uterine injury.
    PLoS ONE 01/2014; 9(5):e96662. · 3.73 Impact Factor
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    ABSTRACT: Women with endometriosis frequently suffer from autoimmune inflammatory diseases, allergies and asthma. This study was conducted to examine whether the prevalence of allergies is higher in patients with endometriosis than in the control group, and to show potential correlation with endometriosis stages. We evaluated the medical files of 501 women with laparoscopically-diagnosed endometriosis and 188 women without endometriosis enrolled in Yale University Hospital. Main outcome measures used were allergy on medications, complaints of sinus or perennial allergic rhinitis, asthma, family history of allergic disease, and correlation with stages of endometriosis. Our results indicated that the overall risk of women with endometriosis and positive history of allergies was 4.28 (95% CI, 2.9-6.3) (p < 0.001). Significant excesses were identified for medications, sinus allergic rhinitis, and asthma; also, women with endometriosis were significantly more likely to report a positive family history of allergies. Overall, our study indicated a link between endometriosis and increased risk of allergic autoimmune disorders that should further be explored.
    Journal of Obstetrics and Gynaecology 04/2012; 32(3):291-3. · 0.55 Impact Factor
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    ABSTRACT: Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.
    Reproductive sciences (Thousand Oaks, Calif.) 01/2012; 19(6):572-9. · 2.31 Impact Factor
  • Hakan Cakmak, Emre Seli
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    ABSTRACT: Fertility preservation in females diagnosed with cancer has become an important area of investigation due to increasing cancer survival rates combined with delayed childbearing. Initial studies using gonadotropin-releasing hormone (GnRH) agonist cotreatment with chemotherapy demonstrated promising results for fertility preservation. If this protective effect of GnRH agonists is confirmed by the ongoing prospective randomized clinical trials, GnRH agonist cotreatment may become valuable option for fertility preservation in reproductive-age women undergoing chemotherapy. Thus, ovarian protection may enable the preservation of future fertility in survivors and, in addition, prevent other adverse effects of premature menopause, such as bone density loss, sexual dysfunction, and vasomotor symptoms. KeywordsGonadotropin-releasing hormone agonist-Fertility preservation-Cancer and fertility-GnRH in fertility-GnRH treatment with chemotherapy-Chemotherapy and GnRH treatment
    12/2011: pages 145-157;
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    ABSTRACT: The diagnosis of uterine dehiscence in the early second trimester by ultrasonography is rare and its effect on pregnancy outcome is unclear. An asymptomatic woman presented for anatomy survey in the 19th week of pregnancy. Uterine dehiscence at the site of previous hysterotomy was diagnosed by ultrasound scan. She was admitted to the hospital for expectant management and eventually opted for termination of pregnancy in the 22nd week of pregnancy. Termination was performed by classical hysterotomy without any complications. Given the increasing cesarean delivery rate and improvements in ultrasound technology, obstetricians should expect to face the management dilemma of antenatally diagnosed uterine dehiscence. The risks of expectant management compared with termination remain theoretical, and timing of delivery and methods of termination are important questions to consider.
    Obstetrics and Gynecology 08/2011; 118(2 Pt 2):497-500. · 4.80 Impact Factor
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    ABSTRACT: The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases.
    Journal of Obstetrics and Gynaecology 02/2010; 30(2):184-6. · 0.55 Impact Factor
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    Hakan Cakmak, Hugh S Taylor
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    ABSTRACT: HOX genes, encoding homeodomain transcription factors, are dynamically expressed in endometrium, where they are necessary for endometrial growth, differentiation, and implantation. In human endometrium, the expression of HOXA10 and HOXA11 is driven by sex steroids, with peak expression occurring at time of implantation in response to rising progesterone levels. However, the maximal HOXA10 and HOXA11 expression fails to occur in women with endometriosis. In endometriosis, altered progesterone receptor expression or diminished activity may lead to attenuated or dysregulated progesterone response and decreased expression of progesterone-responsive genes including HOX genes in the eutopic endometrium. In turn, other mediators of endometrial receptivity that are regulated by HOX genes, such as pinopodes, alphavbeta3 integrin, and IGFBP-1, are downregulated in endometriosis. HOXA10 hypermethylation has recently been demonstrated to silence HOXA10 gene expression and account for decreased HOXA10 in the endometrium of women with endometriosis. Silencing of progesterone target genes by methylation is an epigenetic mechanism that mediates progesterone resistance. The relatively permanent nature of methylation may explain the widespread failure of treatments for endometriosis-related infertility.
    Seminars in Reproductive Medicine 01/2010; 28(1):69-74. · 3.21 Impact Factor
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    Hakan Cakmak, Hugh S Taylor
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    ABSTRACT: Implantation is a complex initial step in the establishment of a successful pregnancy. Although embryo quality is an important determinant of implantation, temporally coordinated differentiation of endometrial cells to attain uterine receptivity and a synchronized dialog between maternal and embryonic tissues are crucial. The exact mechanism of implantation failure is still poorly understood. This review summarizes the current knowledge about the proposed mechanisms of implantation failure in gynecological diseases, the evaluation of endometrial receptivity and the treatment methods to improve implantation. The absence or suppression of molecules essential for endometrial receptivity results in decreased implantation rates in animal models and gynecological diseases, including endometriosis, hydrosalpinx, leiomyoma and polycystic ovarian syndrome. The mechanisms are diverse and include abnormal cytokine and hormonal signaling as well as epigenetic alterations. Optimizing endometrial receptivity in fertility treatment will improve success rates. Evaluation of implantation markers may help to predict pregnancy outcome and detect occult implantation deficiency. Treating the underlying gynecological disease with medical or surgical interventions is the optimal current therapy. Manipulating the expression of key endometrial genes with gene or stem cell-based therapies may some day be used to further improve implantation rates.
    Human Reproduction Update 01/2010; 17(2):242-53. · 9.23 Impact Factor
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    ABSTRACT: Protein kinase B (PKB/Akt), a serine/threonine kinase, regulates the function of many cellular proteins involved in apoptosis and proliferation. It was postulated that there is a higher Akt activity in endometriosis compared with normal endometrium, and that oestrogen may be one of the factors responsible for the high Akt activation in endometriotic cells. Phospho-Akt (pAkt) concentrations in normal, eutopic and ectopic endometrial tissues were compared by immunohistochemistry, and a higher pAkt immunoreactivity was revealed in eutopic and ectopic endometrium compared with normal endometrium, in vivo. Higher Akt phosphorylation in stromal cells from eutopic endometrium was observed, when compared with normal, in vitro (P < 0.05). Akt phosphorylation was rapidly (2-10 min) stimulated when endometrial stromal cells from normal and endometriosis patients were treated with 17 beta-oestradiol. In endometrial stromal cells from the endometriosis group, ICI 182,780 (ICI, a specific oestrogen receptor antagonist) failed to antagonize the effect of oestradiol when combined with oestradiol, and revealed a stimulatory effect on Akt phosphorylation when given alone (P < 0.05). In conclusion, since Akt affects cell survival, it is suggested that increased Akt phosphorylation may be related to the altered apoptosis/proliferation harmony in endometriosis, and therefore Akt may play a critical role in the pathogenesis of endometriosis.
    Reproductive biomedicine online 12/2009; 19(6):864-71. · 2.68 Impact Factor
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    ABSTRACT: Recent studies reported that endometriosis could behave as a neoplasmatic process. The purpose of this study is to investigate the family risk of ovarian, colon and prostate cancer in women with endometriosis. A search of medical records at the Yale New Haven Hospital from 1996 to 2002 identified 348 women with endometriosis and 179 women without endometriosis. All the cases were diagnosed by laparoscopy. Demographic characteristics were evaluated in women with positive or negative family history of cancers in women with endometriosis. The overall risk of patients with endometriosis and positive family history of cancers was 7.7 (95% confidence interval 3.8-15.7) (chi(2)=39.8, P<0.001). Significant excess was observed for ovarian cancer in first- and second-degree relatives (OR=10.5, 95% CI (2.5-44.2), chi(2)=14.3, P<0.001), colon cancer (OR=7.5, 95% CI (2.7-21.1), chi(2)=18.2, P<0.001) and prostate cancer (OR=4.5, 95% CI (14-15.3), chi(2)=6.1, P<0.001). We found similar results in first- and second-degree relatives with ovarian and colon cancer. Moreover, we found similar results regarding the demographic characteristics in women with positive family history of cancers and in women with negative history. These data suggest a familial association of endometriosis with ovarian, colon and prostate cancers. This evidence could support the genetics and molecular similarities between endometriosis and cancer. Future studies will be important to determine a clear genetic link between endometriosis and cancer.
    Surgical Oncology 03/2009; 19(1):33-7. · 2.14 Impact Factor
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    ABSTRACT: The aim of this investigation was twofold: first, to demonstrate an association between endometriosis, ABO blood groups and Rhesus factor and, second, to show potential correlation of ABO blood group and stages of endometriosis. Two hundred and thirty-one women with endometriosis and 166 infertile women without endometriosis were studied retrospectively at the Yale University Hospital. All the cases were diagnosed by laparoscopy and in all of them ABO blood groups and Rhesus factor were determined by standard techniques. Women with endometriosis were divided into two groups according to the stage: Group 1 included 124 cases with stages I and II, and Group 2, 107 women with stages III and IV. Statistical methods included chi(2) and odds ratios (95% CI). The identified distribution of ABO and Rh blood groups in women with endometriosis differed significantly from that of the women without endometriosis [chi(2) = 26.27, (P < 0.001); chi(2) = 18.71, (P < 0.001), respectively]. The blood group A was more predominant in women with endometriosis, while blood group O was less predominant. The overall risk of women with endometriosis and A blood group was 2.89 (95%CI, 1.85-4.52). No significant difference was detected in ABO and Rh blood groups in women with endometriosis according to the severity of disease. Women with endometriosis have a 2.9-fold increased risk in the A blood group distribution. The role of blood groups in the development of endometriosis remains to be determined.
    Archives of Gynecology 03/2009; 280(6):917-9. · 0.91 Impact Factor
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    ABSTRACT: Endocrine and immune systems are among the most essential regulators of endometrial physiology, and immune-endocrine interactions are likely to be involved in the pathogenesis of endometriosis. Endometriosis is an inflammatory, estrogen-dependent disease defined by the presence of viable endometrial tissue outside the uterine cavity. Impaired immune response that results in inadequate removal of refluxed menstrual debris has been proposed as a possible causative factor in the development of endometriosis. Moreover, decrease in spontaneous apoptosis of endometrium is the other theory proposed for the development of endometriosis. Endometriotic tissues respond to sex steroids aberrantly and behave differently compared to endometrium in addition to their ability to produce local estrogen. The effects of estrogen on distinct intracellular signaling pathways including MAPK, PI3K/AKT and NF-kappa B may take a role in enhanced endometrial cell survival, altered immune response, and differential cytokine and chemokine expression in endometriosis. Better understanding of immune-endocrine interactions will set the stage for effective immune-targeted therapies not only for endometriosis but also for other endometrial diseases such as adenomyosis, recurrent reproductive failure and implantation-related infertility.
    Frontiers in bioscience (Elite edition) 02/2009; 1:429-43.
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    ABSTRACT: Endometriosis is an estrogen-dependent disease characterized by the presence of endometrial tissue outside of the uterine cavity, causing pelvic pain and infertility in 10% of reproductive-aged women. It is unclear why ectopic endometrium remains viable in only a subset of women. ERK1/2 plays key intracellular roles in activating cellular survival and differentiation processes. We sought to determine ERK1/2 activity in patients with endometriosis and its possible roles in regulating endometrial cell survival. ERK1/2 phosphorylation and expression throughout the menstrual cycle were evaluated in vivo in normal and endometriotic human endometrium, and in vitro techniques assessed the steroidal regulation of ERK1/2 and its effect on endometrial cell survival. Total ERK1/2 remained constant in normal and endometriotic endometrium throughout the menstrual cycle. Phospho-ERK1/2 was high in the late proliferative and secretory phases in normal endometrium (P < 0.05). In endometriotic glandular cells, there was no cyclical variation in phospho-ERK1/2. In endometriotic stromal cells, there was also a reduction in phospho-ERK1/2 variation, with higher levels in the early-mid secretory phase (P < 0.05). In cultured endometrial stromal cells (ESCs), estrogen plus progesterone increased ERK1/2 phosphorylation within 15 min (P < 0.05). Although estrogen alone did not induce ERK1/2 phosphorylation in normal ESCs, there was a significant response to estrogen in ESCs isolated from eutopic endometriotic endometrium (P < 0.05). ERK1/2 inhibition in ESCs reduced proliferation and increased apoptosis (P < 0.05). Abnormally high levels of ERK1/2 activity may be involved in endometriosis, possibly by stimulating endometrial cell survival.
    Journal of Clinical Endocrinology &amp Metabolism 06/2008; 93(9):3532-40. · 6.43 Impact Factor
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    ABSTRACT: A group of 140 women with a body mass index (BMI) < or = 24 kg/m(2) undergoing 291 cycles was compared with a group of 138 women with a BMI >24 kg/m(2) in 291 cycles, with respect to duration of ovarian stimulation and dose of gonadotrophin, number of oocytes collected, cleavage and implantation rate, clinical pregnancy, miscarriage and delivery rates. Patients with a BMI > 24 kg/m(2) demonstrated a significant decrease in the number of follicles after stimulation (P = 0.01), a comparative increase in the number ampoules of gonadotrophin used (P = 0.03) and a lower number of eggs collected (P = 0.05). The mean number of embryos on days 1, 2 and 3 was significantly lower in the group with BMI > 24 kg/m(2) (P < 0.001). No significant difference was found in clinical pregnancy and miscarriage rates between the two groups. In spite of the lower response in women with BMI > 24 kg/m(2), the delivery rate per retrieval was not different (24.6 versus 24.8%). These results indicate a lower stimulation response in women with elevated BMI, but no adverse effect on IVF outcome. In relation to wellbeing, however, it is recommended that patients with a high BMI reduce their weight before IVF treatment.
    Reproductive biomedicine online 06/2008; 16(6):778-83. · 2.68 Impact Factor
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    ABSTRACT: JNK(c-Jun N-terminal kinase) is one of the main types of mitogen-activated protein kinases. JNK modulates inflammation and apoptosis in response to stress. Our hypothesis is that temporal and spatial changes in JNK activity regulate inflammation in human endometrium and that fluctuation in estrogen and progesterone levels may play a role in JNK activation. Therefore, we aimed to determine total-(t-) and active-(phosphorylated, p-) JNK expression in endometrial tissues in vivo by immunohistochemistry, and in vitro by immunocytochemistry and Western blot analysis. Immunohistochemistry revealed moderate cytoplasmic and nuclear t-JNK immunoreactivity, and mostly nuclear p-JNK immunoreactivity throughout the menstrual cycle and early pregnancy. The highest p- and t-JNK immunoreactivity was detected in late secretory phase (P < 0.05). We observed that endometrial stromal cell (ESC)s showed a significant increase in p-JNK expression following 48 h of estrogen combined with progesterone (E(2) + P(4)) withdrawal from the culture conditions, compared to control and non-withdrawal groups (P < 0.05). Upon treatment with JNK inhibitor SP600125, we observed a significantly decreased interleukin (IL)-8 level (P < 0.05) in the presence and absence of E(2). These results demonstrate that JNK expression increases during the late secretory phase when the inflammatory response is highest. Inhibition of IL-8 expression by SP600125 suggests that JNK is involved in regulation of proinflammatory mediators of endometrium.
    Histochemie 05/2008; 130(4):761-71. · 2.61 Impact Factor
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    ABSTRACT: To investigate the familial aggregation and the risk of endometriosis among the female relatives of women with endometriosis. We also compared the epidemiologic characteristics of women with and without family history of endometriosis. A total of 485 women with endometriosis and 197 infertile women without endometriosis underwent surgical investigation between August 1996 and February 2002. The relative risk of endometriosis in a first-degree relative and the association between potential risk factors was estimated by chi2 and by crude adjusted odds ratios (95% CI). Endometriosis was identified in 9.5% of first-degree relatives of women with endometriosis versus only 1% of controls. The odds ratio for endometriosis in a first-degree relative was 10.21 (95% CI 2.45-42.5; P<0.001). In 3.9% of cases women with endometriosis reported that their mother had been diagnosed with endometriosis and 5.6% of cases that at least one sister had been diagnosed. Compared to the control group the odds ratio for the mother having endometriosis (7.99, 95% CI 1.06-60.1) or at least one sister having (11.55, 95% CI 1.56-85.59) were significantly elevated. Among women with endometriosis who reported a family history of endometriosis, and women with endometriosis who did not report a family history of endometriosis, there were no differences in demographic characteristics, body habitus, or menstrual parameters. Women with endometriosis have a tenfold increased risk of endometriosis in their first-degree relatives.
    Archives of Gynecology 05/2008; 278(6):507-11. · 0.91 Impact Factor
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    ABSTRACT: Few studies examining the association of endometriosis with the risk of breast cancer. Our goal was to investigate the familial risk of breast cancer in women with endometriosis. Retrospective study. University-based endometriosis referral center. Three hundred fifty-two women with endometriosis and 180 infertile women without endometriosis were studied using laparoscopy between August 1996 and February 2002. The endometriosis group was further subdivided into a group of women with 94 positive and 268 negative family histories of breast cancer. The overall risk of familial breast cancer among first- and second-degree relatives in patients with endometriosis and the association between potential risk factors was estimated by chi(2) and by crude adjusted odds ratios (95% CI). Positive family history of breast cancer was detected in (26.7%) 94/352 of endometriosis group and in (5%) 9/180 of controls. The relative risk of women with endometriosis and positive family history of breast cancer was (OR=6.9 (95% CI, 3.4-14.1), chi(2)=34.6, P<0.001). Endometriosis was associated with the risk of first-degree relatives of breast cancer (OR=5.69 (95% CI, 2.4-13.3), P<0.001). Moreover, endometriosis was significantly associated with the risk of breast cancer in mothers (OR=6.3 (95% CI, 2.2-17.8), P<0.001) and in maternal aunts (OR=5.9 (95% CI, 1.3-72.9), P<0.001). The two groups are similar in age, race height, main complaints, age of menarche, cycle length, days of flow, estimated blood loss, stage of endometriosis and the presence of endometrioma. This study found an elevated risk associated with family history of breast cancer among women with endometriosis. A familial clustering interaction with a familial history of breast cancer in women with endometriosis is possible, but should be investigated further.
    Surgical Oncology 05/2008; 17(4):289-93. · 2.14 Impact Factor
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    ABSTRACT: The association between demographic factors, menstrual and reproductive characteristics, and clinical profile for women with endometriosis was analyzed in a retrospective case-control study. Over a 6-year period, 535 women with endometriosis and 200 infertile women without endometriosis, studied by laparoscopy or laparotomy, were evaluated. Information was then collected in a uniform manner from the patients' medical records. Statistical methods included chi(2) and Mann-Whitney U test. The factors associated with an increased risk for endometriosis include lower body weight, alcohol use (chi(2) = 8.8; P < 0.003), early menarche (chi(2) = 5.08; P < 0.024), shorter cycle length (chi(2) = 13.06; P < 0.001), and heavier menstrual cycles. Pelvic pain was present in 79.1% of women with endometriosis, dysmenorrhea in 70.2%, and dyspareunia in 49.5%. These symptoms were statistically significantly higher in comparison with the infertile women without endometriosis (P < 0.001). Moreover, we found that women with endometriosis had fewer prior pregnancies, elective abortions and ectopic pregnancies compared to women seeking care for infertility, who did not have endometriosis. Interestingly, women with endometriosis were significantly more likely to report a family history of cancer compared to women in control group (chi(2) = 78.2; P < 0.001). Body habitus, personal habits and menstrual characteristics are all strongly associated with the development of endometriosis. There may also be an association between family history of cancer and the development of endometriosis.
    Archives of Gynecology and Obstetrics 05/2008; 277(5):389-93. · 1.33 Impact Factor
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    ABSTRACT: There are conflicting data concerning endometriosis and spontaneous abortion (SAB). The aim of the present study was to evaluate if there was any association between endometriosis and SAB. Moreover, we investigated risk factors in women with endometriosis and SAB. The medical files of 457 married women with endometriosis and 200 infertile women without endometriosis were studied retrospectively. All cases were diagnosed by laparoscopy. Data concerning demographic variables and menstrual characteristics were recorded from 226 women with endometriosis, which were divided into two groups. Group 1 included 126 cases with endometriosis and SAB, and Group 2 comprised 100 parous women with endometriosis and without SAB. Statistical comparisons between groups were made using the chi(2) test and odds ratios (OR) and 95% confidence intervals (CI). The proportion of SAB was significantly higher in women with endometriosis than in infertile women without endometriosis (126/457 (27.6%) vs. 36/200 (18.0% ); OR = 1.7, 95% CI 1.1 = 2.6; p = 0.01). The frequency of nulligravid women was significantly higher in women with endometriosis than in the control group (OR = 1.9, 95% CI 1.4 - 2.81; p = 0.001). Mean age, age at onset of endometriosis, race, height, weight, body mass index, medical history of allergies, and family histories of endometriosis and cancer were similar in women with endometriosis and SAB and in parous women with endometriosis but without SAB. Moreover, the two groups were similar in age at menarche, length of cycle, duration and amount of flow, and the severity of disease. The incidence of infertility was significantly higher in women with SAB (p < 0.001). These data suggest but do not prove that the risk of SAB is increased in women with endometriosis. The epidemiological risk factors of endometriosis are not associated with an increase in the abortion rate.
    Gynecological Endocrinology 05/2008; 24(4):194-8. · 1.30 Impact Factor
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    ABSTRACT: To analyze a hypothesis regarding the pathogenesis of endometriosis. Retrospective study. Two academic endometriosis referral centers. We evaluated operative and pathologic reports of 251 women who underwent laparoscopic or laparotomy treatment of endometrioma from August 1996 to February of 2002 at Yale University School of Medicine and at the University of Crete Department of Obstetrics and Gynecology. Laparascopic examination. Statistical methods included chi(2) and Mann-Whitney U tests measuring incidence of right- vs. left-sided endometria. One hundred seventy patients from Yale University and 81 Greek patients participated in this study. Endometrioma was significantly more frequent in the left ovary (139 of 206 [67.4%]) than in the right ovary (67 of 206 [32.6%]; odds ratio [OR] = 4.3; 95% confidence interval [CI) 2.9-6.5; chi(2) = 48.9) and significantly different from the expected proportion of 50% (chi(2) = 25.2). When bilateral endometriomas were included, 62.1% (184 of 296) were left-sided and 37.15 (112 of 296) were right-sided (OR = 17.5; 95% CI 1.9-3.8; chi(2) = 34.1). Dilated ovarian veins in were found in 22 (68.7%) of 32 Greek cases with endometrioma. All 20 women with left endometrioma had left ovarian vein dilated. We suggest a new mechanical theory of implication, the female varicocele theory, which could play an important role in the development of ovarian endometriosis or endometriomas.
    Fertility and sterility 04/2008; 91(4):975-8. · 3.97 Impact Factor

Publication Stats

409 Citations
94.99 Total Impact Points

Institutions

  • 2005–2012
    • Yale University
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      New Haven, CT, United States
  • 2010
    • University of Crete
      • Department of Obstetrics and Gynaeocology
      Retimo, Crete, Greece
  • 2005–2010
    • Yale-New Haven Hospital
      • Reproductive Endocrinology Services
      New Haven, Connecticut, United States
  • 2006
    • Trakya University
      Adrianoupolis, Edirne, Turkey