Tehran University Medical Journal

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Background: Polycystic ovary syndrome (PCOS) is a common cause of ovulation insufficiency and then infertility. Therapeutic options to induce ovulation in anovulatory PCOS patients are clomiphene citrate, metformin, tamoxifen, dopamine agonists (bromocriptin), Gonadotrophin and laparoscopic ovarian electrocautery (LOE). Gonadotrophin and LOE are important options in anovulatory clomiphene citrate-resistant patients with PCOS. Literature data regarding compare of the efficacy of these two treatments are few. Therefore we aimed to study the pregnancy rates of these treatments in infertile clomiphene citrate-resistant patients with PCOS. Methods: A randomized clinical trial study was carried out in infertile clomiphene citrate-resistant patients with PCOS, referred to infertility clinic of Mirza Koochackhan Hospital of Tehran University of Medical Science in Tehran, Iran, between 2003 and 2008. Results: A total of 100 patients women were randomly allocated in two groups. There were no differences in age and pimary and secondary infertility duration. In LOE treatment group, eight cases (16%) were pregnant and all delivered at term. in gonadotrophin treatment 14 cases (28%) were pregnant, 10 cases (20%) delivered at term but four cases aborted. The cost in gonadotrophin treatment was significantly more than laparoscopic ovarian diathermy (p<0.001). In logistic regression analysis, age, BMI, cost and kind of treatment had no significant effect on pregnancy rate. Conclusions: Pregnancy and abortion rate in gonadotrophin treatment was more than LOE but the difference was not significant. More studies are needed.

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Background: Human cancer cell lines express human choriogonadotropin (hCG), its subunits and derivatives, regardless of their origin and type. It appears that hCG is a common phenotype in human cancer cell lines. In this research, the effects of hCG targeting monoclonal antibodies (7D9, T18H7 and T8B12) on human cancer cell lines were evaluated.
Methods:  Monoclonal antibody secreting hybridomas were proliferated and injected intraperitoneally to Balb/C mice after treatment with pristine. Two weeks later, ascites fluid was collected. Purification of aforementioned antibodies from ascites fluid was performed using G-protein affinity followed by ion exchange chromatography. SDS-PAGE and ELISA confirmed the structure and functional integrity of the purified antibodies, respectively. Two human cancer cell lines "Hela" and "MDA" were treated by the purified antibodies. Three days later, different wells were imaged and the cells counted.
Results:  SDS-PAGE gel (None-reducing) indicated consistency of band migration patterns with control antibodies. ELISA test using hCG antigens indicated that the produced antibodies could detect hCG antigens. Cell lines were cultured and treated with different concentrations of each antibody. Counting and imaging different wells of treated plates, indicated that 7D9 antibody had a more significant (P<0.01) cytotoxic effect on cancer cell lines than the control cells.
Conclusion: HCG targeting monoclonal antibodies can be used for targeted cancer therapy, as human cancer cells express hCG gene. 7D9 antibody that exhibits protease activity is a proper candidate for this purpose, as it possesses both antagonistic and enzymatic properties.

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Background: Endothelial dysfunction can influence fertility rate in women with polycystic ovary syndrome (PCOS) as flow mediated dilatation (FMD) is impaired in patients with the disease. The aim of this study was to compare two methods of ovulation induction by letrozole or letrozole plus human menopausal gonadotropins (HMGs) in infertile women with PCOS who were resistant to clomiphene citrate based on brachial artery ultrasound findings.

Methods: In this double -blind randomized clinical trial, 59 infertile women who had the inclusion criteria for PCOS were evaluated in the Infertility Clinic of Shariati Hospital in Tehran, Iran in 2010-2011. The patients were assigned to two letrozole and letrozole plus HMG groups and were evaluated for FMD in the brachial artery by transvaginal ultrasonography. Later, the values were recorded and analyzed statistically.

Results: In the letrozole group, infertility treatment was successful in 15 (57.7%) but it failed in 11 (42.3%) patients. In letrozole plus HMG group, the treatment was successful in 18 (54.5%) while it failed in 15 (45.5%) patients. The mean FMD values in the groups with successful and unsuccessful treatment results were 19.42±10% and 18.57±7.2%, respectively, but the difference was not statistically significant (P=0.712). Moreover, the average endometrial thickness in groups with successful and unsuccessful treatment results were 8.4±1.3 mm and 9.8±3.9 mm, respectively but the difference was not significant either (P=0.06).

Conclusion: In infertile women with polycystic ovary syndrome that are resistant to clomiphene, letrozole or letrozole combined with gonadotropin can be equally effective for ovulation induction.

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Background: The use of Methotrexate (MTX) is a good and common practice for the treatment of women who were diagnosed early with ectopic pregnancy (EP). The aim of this study is to determine the predictors of treatment failure with a single dose of MTX injection. Methods: In this quasi-experimental research, we studied 70 women with ectopic preg-nancies who were treated with MTX, according to a single dose protocol from 2010 to 2013. EP was diagnosed whenever an intrauterine gestational sac was not identified by transvaginal ultrasonography (TVUS), accompanied by an abnormal rise or plateau in human chorionic gonadotropin (beta-hCG) concentration. Briefly, women with ectopic pregnancies were considered candidates for MTX treatment if they were hemodynami-cally stable did not desire surgical therapy, agreed to weekly follow-up and did not have hepatic, hematologic, or renal disease. A Patient was considered a treatment suc-cess (group 1) if her beta-hCG levels decreased ≤10 m IU/ml after the first dose of MTX. Treatment failure (group 2) was defined as the need for a second or a third dose of MTX or surgery. The following risk factors were compared between the two groups: serum beta-hCG on the days 1 and 4, a ≥ 15% decrease in serum beta-hCG between the days 1-4 of the treatment, age, parity, gravidity, the size of the ectopic mass and the endometrial thickness. Results: The success rate of MTX treatment was 77.1%. There were no significant dif-ferences between the two groups in regard to the age, parity, gravidity, the size of ec-topic mass and the endometrial thickness in vaginal sonography, but the mean serum beta-hCG concentration on days 1 and 4 was lower in the success group than the failure group. We also observed a ≥ 15% decrease in serum beta-hCG in 80.9% of the women from the success group and in 38.5% of the cases whose treatment had failed. The presence of fetal heart activity was seen in only one patient and this patient’s treatment failed. Two patients had previous history of ectopic pregnancy and the treatment of both ended in failure. Conclusion: Among women with ectopic pregnancies who were candidates for MTX treatment, a high serum beta-hCG concentration on the days 1-4 and also a ≤ 15% fall in serum beta-hCG between the days 1-4 treatment, are the most important factors associated with the failure of the treatment with a single dose MTX protocol. It is better to use these factors for making decisions about the initiation of the treatment or the continuation of it.

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Background: Gonadotropins are commonly used for superovulation in human and animals to retrieve more oocyte and increase chance of pregnancy. Ovarian stimulation in assisted reproduction technology produces lower implantation rates per embryo transferred than natural and ovum donation cycles, suggesting suboptimal endometrial development due to the hormones used to recruit more oocytes. Due to the frequent use of gonadotropins in the treatment of infertility in successive periods, the aim of this study was to determine the endometrial changes in response to repeated ovarian stimulation. Methods: This experimental interventional study has done in research center of Hamadan university of medical sciences in 2012. NMRI female mice six weeks old were used in this study and divided into 7 groups (5 each). The mice in group 1, 2, 3 and 4 received 1, 2, 3 and 4 times pregnant mare serum gonadotropin (PMSG) and 48 hours later 7.5 IU human chorionic gonadotrophin (hCG) respectively. For each group were considered a control group which received on time gonadortropin injection. The mouses were killed 13-16 hours after hCG injection and middle part of uterine horn cut for histological study using Hematoxylin and Eosin staining. The parameters that studied were surface epithelium of endometrium, glandular epithelium, and endometrial height and axis of uterine gland. Results: Our results showed that there are no significant differences in glandular epithelium, axis of glands and height of endometrium in experimental groups (P>0.05). The height of surface epithelium showed significant increases after ovarian stimulation in experiment group (P≤0.03). Our results showed that there are no significant differences in glandular epithelium, axis of glands, height of endometrium and height of surface epithelium between control groups and also it's experimental group (P>0.05). Conclusion: Changes in the height of surface epithelium could be one of the reasons for decrease implantation rates with repeated ovarian stimulation.

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Background: Ovarian sex cord-stromal tumors (SCST) account for rare ovarian malignancy. These tumors are 5-8% of all ovarian neoplasms. The most common type of sex cord ovarian tumors is granulosa cell tumor (GCT). In this study our purpose was to have a look at some of clinicopathologic aspects and treatment results of these tumors. Methods: In a retrospective study, all documents of patients with SCST was referred to tumor clinics of Ghaem and Omid Hospitals, from 1998 to 2008. The data of patients were collected and analyzed. Results: In 39 (5.9) of the 398 cases, ovarian malignancies was present in SCST. Eight Patients omitted from the study because there were not enough data for them. The commonest pathology was adult granulosa cell tumor in 25 patients (80.6%). Two patients (8.33%) had juvenile granulosa cell tumor, they were 25 and 38 years old. At time of diagnosis, 27 cases (87.1%) were in early stages (stage I). Mean age of patients was 41 years (range 16-76 years) at time of diagnosis of disease. Surgical staging of cancer was performed in 14 patients (46.7%). We did fertility sparing surgery in 12 patients (40%). Two patients were pregnant after surgery. 17 patients (54.80%) did not receive chemotherapy. Three patients (9.7%) received radiotherapy. Overall survival rates were 95% at both 2 years and 5 years. Longer survival had correlation with early stages of disease (P= 0.002). Age, conservative surgery and chemotherapy had no correlations with survival. Conclusion: The prognosis of SCST is almost good. Most of the patients were diagnosed in early stage of disease. In sex cord ovarian tumor, the only factor that have a full effect on survival, is stage of the disease. If the patients desire to preserve fertility, we can do fertility sparing surgery with minimal effect on survival.

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Background: Swyer syndrome is a type of hypogonadism with 46,XY karyotype. This syndrome was named by Gerald Swyer, an endocrinologist. It leads to a female with normal internal genitalia (uterus, fallopian tubes, cervix, vagina), but instead of ovaries, they have non functional ovary (streak gonads). Also, they have absence of puberty because of gonadal  digenesis. The current practice is to proceed gonadectomy once the diagnosis is made due to the fact that the risk of malignant transformation is high in dysgenetic gonad. In addition, hormonal replacement therapy after surgery is acceptable.

Case Presentation: We present a case of gonadoblastom in right ovary in a Swyer syndrome who referred to the department of Gynecology Oncology at Ghaem Hospital, Mashhad University, Iran in 2015 for evaluation of abdomino-pelvic distention. She was a 18-year-old female with 46, XY karyotype and poor secondary sexual character and normal external genitalia. She suffered of abdominal pain. In palpation of the abdomen, an irregular mobile mass was detected in left lower quadrant. The ultrasound revealed uterine size approximate dimensions 3×2 cm (infantile) and a 19 cm pelvic mass heterogeneous and multi-loculated in left side of the pelvic cavity with possible origin of the left ovary. In addition, in right pelvic fossa, a mass about 6 cm was detected. CT-Scan showed a pelvic mass with overall dimensions of 10 cm with vicinity to the left iliac vessels, modest amounts of ascities along with evidence of peritoneal dissemination (seeding). In laparotomy we observed massive ascities and a 20 cm solid mass in left ovary and a small mass in right ovary and involvement para aortic lymph node. Pathological report indicated as stage III of dysgerminoma in left ovary and gonadoblastom in right ovary.

Conclusion: This case is presented because it could have excellent prognosis if not missed opportunities of early recognizing and furthermore adequate treatment with gonadectomy.

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