Further delineation of familial polycystic ovary syndrome (PCOS) via whole-exome sequencing: PCOS-related rare FBN3 and FN1 gene variants are identified.

AIM: To identify pathogenic rare coding Mendelian/high-effect size variant(s) by whole-exome sequencing in familial polycystic ovary syndrome (PCOS) patients to elucidate PCOS-related pathways. METHODS: Twenty women and their affected available relatives diagnosed with PCOS according to Rotterdam criteria were recruited. Whole-exome sequencing on germ-line DNA from 31 PCOS probands and their affected relatives was performed. Whole-exome sequencing data were further evaluated by pathway and chemogenomics analyses. In-slico analysis of candidate variants were done by VarCards for functional predictions and VarSite for impact on three-dimensional (3D) structures in the candidate proteins. RESULTS: Two heterozygous rare FBN3 missense variants in three patients, and one FN1 missense variant in one patient from three different PCOS families were identified. CONCLUSION: We identified three novel FBN3 and FN1 variants for the first time in the literature and linked with PCOS. Further functional studies may identify causality of these newly discovered PCOS-related variants, and their role yet remains to be investigated. Our findings may improve our understanding of the biological pathways affected and identify new drug targets.

Progranulin and tumor necrosis factor-alpha in lean polycystic ovary syndrome patients.

OBJECTIVE: In this study, levels of progranulin (PGRN) and tumor necrosis factor-alpha (TNF-α) were measured to detect the presence of inflammation in lean polycystic ovary (PCOS) patients. METHODS: 40 lean PCOS patients were assessed by Rotterdam criteria. Forty healthy women with regular menstrual cycles and without biochemical and clinical hyperandrogenism were involved in our study. Blood samples were taken from the patient and control groups for the measurement of progranulin (PGRN), tumor necrosis factor-alpha (TNF-α), lipid parameters, glucose, insulin, and other hormones. RESULTS: Serum PGRN and TNF-α levels were significantly higher in patients with lean PCOS, compared with the control group (p = .037, p = .041). PGRN levels were positively correlated with TNF-α levels in lean PCOS patients. CONCLUSION: PGRN is known as a ligand for the TNF-α receptor. PGRN level increase in lean PCOS patients may be due to inhibiting the inflammatory effects of TNF-α. To observe the PGRN and TNF-α connection in obesity, further study is needed in obese PCOS patients and obese control groups.

Decision regret and associated factors following oocyte cryopreservation in patients with diminished ovarian reserve and/or age-related fertility decline.

PURPOSE: To evaluate the prevalence and factors associated with decision regret following oocyte cryopreservation (OC) in women with diminished ovarian reserve (DOR) and/or age-related fertility decline (ARFD). METHODS: A cross-sectional survey study was conducted to five hundred fifty-two women with DOR and/or ARFD who underwent OC between 2014 and 2019 in two private-assisted reproductive units in Istanbul, Turkey. Decision regret was measured using the validated Decision Regret Scale (DRS). RESULTS: The median and mean DRS scores were 10 (interquartile range: 25) and 13.4 (SD: 13.2, range 0-70), respectively. Eighty-five (52.5%) women reported mild regret and 26 (16%) had moderate to severe regret. Decision regret was inversely associated with the belief in fate regarding childbearing and trust in the efficacy of OC. CONCLUSIONS: The prevalence of severe decision regret among patients with DOR and/or ARFD undergoing OC is low. Women who had belief in fate and trusted in the efficacy of oocyte cryopreservation had significantly lower decisional regret.

Assessment of the Relationship Between Serum High Molecular Weight Adiponectin Hormone Levels and Insulin Resistance in Patients with Polycystic Ovary Syndrome.

The purpose of this study was to assess the rate of insulin resistance (IR) and the relationship between IR and high-molecular weight adiponectin (HMWA) in patients with polycystic ovary syndrome (PCOS). A cross sectional study involving 43 women with PCOS and 39 normal women was carried out over a period of nine months. Fasting glucose and insulin levels, lipid parameters and androgen levels were measured in all serum samples. HMWA was determined by enzyme-linked immunosorbent assay and IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The IR was more prevalent in the PCOS group than in the controls (p=0.002). Dehydroepiandrosterone sulfate, sex hormone binding globulin, free androgen index, total testosterone, insulin, and HOMA-IR levels were significantly higher in the PCOS group as compared to the control group (all p<0.05). Moreover, HMWA was significantly lower and negatively correlated with the clinical and biochemical hyperandrogenism in the PCOS group. HMWA and HOMA-IR were also associated with triglyceride, body mass index, and fat mass in this group. ROC curve analyses demonstrated that the AUC, indicative of the HMWA value for discriminating PCOS with IR, was 0.725, with a confidence interval of 0.615-0.835 (p=0.001). The serum HMWA levels are lower in patients with PCOS, which suggest that HMWA might be involved in the pathogenesis of PCOS. We also conclude that HMWA might be a strong determinant of IR in PCOS patients.

A rare cause of acute abdominal pain in children: Isolated tubal torsion; a case series.

Isolated tubal torsion -a rare cause of acute abdomen in children-is usually difficult to diagnose because of non-specific findings. Surgical salphingectomy is required in delayed diagnosis in most cases. Three sexual inactive adolescents diagnosed in isolated tubal torsion (ITT) were discussed for its diagnostic features and surgical management. Laboratory tests and radiological studies including ultrasonography (US), color doppler ultrasound were performed in all patients after evaluation for acute lower abdominal pain in emergency department and they underwent surgical intervention with laparotomy (n:2) and laparoscopy (n:1). One of the patients in this study had salpingectomy. Detorsion of the fallopian tube and cyst excision were performed in the remaining two patients who also had paratubal cysts. There was no recurrence in these patients during the follow-up for 3 and 2 years. The isolated tubal torsion should be kept in mind and early surgical management is essential in order to preserve fallopian tube because of its importance in fertility.

Regret around fertility choices is decreased with pre-treatment counseling in gynecologic cancer patients.

PURPOSE: Data have demonstrated an association between regret and lack of fertility counseling among patients undergoing treatment for non-gynecologic cancers. We sought to determine if fertility-related regret is reduced with pre-treatment counseling or fertility-sparing surgery (FSS) in patients with gynecologic cancers. METHODS: A cross-sectional survey was administered to 593 reproductive-age survivors (18-40 years old at diagnosis) of localized cervix, ovarian, or endometrial cancers that were eligible for FSS. A validated decision regret score was used to evaluate regret in patients. RESULTS: Four hundred seventy women completed the survey. Forty-six percent received pre-treatment counseling about treatment's effects on fertility. Having received counseling (adjusted ß-coefficient of -1.24, 95 % CI = -2.29 to -0.18, p = 0.02), satisfactory counseling (adjusted ß-coefficient of -2.71, 95 % CI = -3.86 to -1.57, p < 0.001), and FSS (adjusted ß-coefficient of -1.26, 95 % CI = -2.39 to -0.14, p = 0.03) were associated with lower regret post-treatment, after adjusting for age. Time since diagnosis, prior parity, socioeconomic status and cancer type were not associated with regret (p > 0.05). While 50 % of women reported desiring more children after diagnosis, desire for children after treatment was associated with increased regret (adjusted ß-coefficient of 3.97, 95 % CI = 2.92-5.02, p < 0.001). CONCLUSIONS: Though less than half of study participants received counseling about the effect of cancer treatment on future fertility, both fertility counseling and FSS were associated with decreased regret in reproductive-aged women with gynecologic cancers. The desire for more children after treatment was associated with increased regret. IMPLICATIONS FOR CANCER SURVIVORS: Inquiring about fertility desires and providing counseling regarding reproductive outcomes following cancer treatment should be implemented as part of the treatment process.

Oocyte Cryopreservation as a Preventive Measure for Age-Related Fertility Loss.

The increased desire to achieve higher educational, career, or financial goals and not having met a suitable partner are the main reasons why women are postponing parenthood to later stages in life. Not being aware of the age-related decline in fertility and the presence of novel and effective fertility preservation strategies are contributing factors to the increased incidence of childlessness at later stages of life. Oocyte cryopreservation has recently been introduced as a means of increasing the probability of motherhood at advanced ages, should attempts at natural conception fail. It is likely to be the most effective when performed in patients younger than 35 years with a good ovarian reserve. Preconceptional counseling of women by medical professionals, education of young adolescents at schools, organization of public health campaigns, and presentation of fertility health information through the media are strategies suggested to increase public awareness on the age-related decline in fertility and avoid its possible consequences.

Sexual satisfaction and quality of life in survivors of localized cervical and ovarian cancers following fertility-sparing surgery.

OBJECTIVE: To determine if sexual satisfaction and sexual quality of life (QOL) are different in survivors of localized cervical and ovarian cancers who undergo fertility-sparing surgery (FSS) as compared with standard surgery. METHODS: 470 survivors of localized cervical and ovarian cancers diagnosed between the ages of 18-40 were recruited from the California Cancer Registry to complete a cross-sectional survey. Validated questionnaires were used to assess sexual satisfaction and sexual QOL. RESULTS: 228 women with localized cervical cancer and 125 with localized ovarian cancer completed the survey. In the cervical cancer group, 92 underwent FSS. Compared with the 84 women who did not undergo FSS (had a hysterectomy, but retained at least one ovary), there was no significant difference in sexual satisfaction or sexual QOL mean scores in women who maintained their uterus (cold-knife cone or trachelectomy), after controlling for age and menopausal status. 82 women with ovarian cancer underwent FSS. Compared with the 39 women that had a bilateral salpingo-oophorectomy, we found no significant differences in sexual satisfaction or sexual QOL in women who maintained at least one ovary (USO or cystectomy), after controlling for age and menopausal status. CONCLUSIONS: While FSS may allow for post-treatment fertility, it may not confer a significant benefit with regard to sexual satisfaction or sexual QOL. Thus, the decision to perform FSS should not be dictated based on preservation of sexual functioning.

Age-specific probability of live birth with oocyte cryopreservation: an individual patient data meta-analysis.

OBJECTIVE: To estimate age-specific probabilities of live birth with oocyte cryopreservation in nondonor (ND) egg cycles. DESIGN: Individual patient data meta-analysis. SETTING: Assisted reproduction centers. PATIENT(S): Infertile patients undergoing ND mature oocyte cryopreservation. INTERVENTION(S): PubMed was searched for clinical studies on oocyte cryopreservation from January 1996 through July 2011. Randomized and nonrandomized studies that used ND frozen-thawed mature oocytes with pregnancy outcomes were included. Authors of eligible studies were contacted to obtain individual patient data. MAIN OUTCOME MEASURE(S): Live birth probabilities based on age, cryopreservation method, and the number of oocytes thawed, injected, or embryos transferred. RESULT(S): Original data from 10 studies including 2,265 cycles from 1,805 patients were obtained. Live birth success rates declined with age regardless of the freezing technique. Despite this age-induced compromise, live births continued to occur as late as ages 42 and 44 years with slowly frozen and vitrified oocytes, respectively. Estimated probabilities of live birth for vitrified oocytes were higher than those for slowly frozen. CONCLUSION(S): The live birth probabilities we calculated would enable more accurate counseling and informed decisions for infertile women considering oocyte cryopreservation. Given the success probabilities, we suggest that policy makers should consider oocyte freezing as an integral part of prevention and treatment of infertility.

Breast cancer diagnosis following ovarian stimulation: are the tumours different?

Demographic data and tumour characteristics of 18 patients (study group) diagnosed with breast cancer within 24 months of undergoing ovarian stimulation with either gonadotrophins or clomiphene citrate were evaluated and compared with similar 102 age-matched women diagnosed with breast cancer without prior infertility treatment (control group). Eight out of 17 (47.1%) patients in the study group and 35/95 (36.8%) patients in the control group had positive family history for breast cancer. Median tumour size was similar in the study and control groups (both 1.3 cm). Both groups were comparable regarding tumour histological types and oestrogen receptor, progesterone receptor and Her2/Neu expression status. Albeit not significant, stage 0 tumours were more prevalent in the study group compared with the control group (22.2% versus 10.5%), and there were no stage III tumours in the study group as opposed to 7/95 in the control group. In conclusion, breast cancer diagnosed within the first 2 years following infertility treatment is similar in tumour characteristics compared with those occurring in patients without prior infertility treatment.

Assessment of ovarian stromal artery Doppler characteristics and serum hormone levels in patients with Behçet disease.

PURPOSE: The aim of the study was to examine serum hormone levels, ovarian volume, stromal artery Doppler parameters of patients with Behçet disease (BD) to assess whether there are vascular changes in the gonads of these patients. MATERIALS AND METHODS: Twenty patients with BD and 31 healthy controls aged between 18-45 years were examined in the early follicular phase of the menstrual cycle (day 2-3) with transvaginal ultrasound to evaluate ovarian volume and ovarian stromal artery Doppler parameters. On the same day, blood was drawn for determining serum hormone levels. RESULTS: Patients with BD and the controls were comparable with regard to age and body mass index at study inclusion. Although comparison of the ovarian stromal artery Doppler velocimetric parameters did not show significant differences, resistivity, pulsatility indexes and systolic/diastolic ratio were higher, while peak systolic and end diastolic velocities were lower, in BD patients compared to controls. The mean ovarian volume of patients with BD was smaller than the controls but this difference did not reach statistical significance. There were no statistically significant differences between serum hormone levels of either group. We did not find any correlations between hormone levels and mean ovarian stromal artery Doppler parameters of patients with BD. CONCLUSION: Ovarian stromal artery Doppler parameters of patients with BD did not show any significant differences compared to healthy controls. Therefore, we conclude that ovarian stromal artery is not involved in patients with BD as assessed by transvaginal Doppler ultrasound and serum hormone levels do not differ from the levels of healthy controls.

Who is the best candidate for oocyte cryopreservation research?

Clinical studies of oocyte cryopreservation have gained momentum within the recent years; however, no guidelines have yet been established for patient selection. This article discusses the controversial aspects of selecting candidates for oocyte cryopreservation research.

Ongoing pregnancies from early retrieval of prematurely developing antral follicles after DHEA supplementation.

Two patients with severely diminished ovarian reserve who were refractory to aggressive ovarian stimulation conceived with oocytes from prematurely developing antral follicles after dehydroepiandrosterone supplementation. The first patient had 11 and 14.5 mm, and the second patient had 13 mm antral follicles on cycle days 2 and 3 respectively. In the first case, no ovarian stimulation was performed, while the second case received one dose of gonadotrophins with a gonadotrophin-releasing hormone antagonist. Following very early human chorionic gonadotrophin (HCG) triggering on cycle day 5, when antral follicles reached 15 and 18.5 mm in the first case, and 19 mm in the second case, IVF intracytoplasmic sperm injection treatment resulted in pregnancies in both cases, which are currently ongoing at 35 and 14 weeks of gestation. The results in these patients show that pregnancy can be achieved in poor responder patients with prematurely developing antral follicles following early HCG triggering based on follicle size rather than cycle day, with no or minimal stimulation. Whether DHEA supplementation had any impact on the success of these cycles remains to be determined.

Assessment of ovarian reserve and Doppler characteristics in patients with multiple sclerosis using immunomodulating drugs.

OBJECTIVE: There is limited data about fertility in multiple sclerosis (MS) patients using immunomodulating drugs and no data exists regarding the ovarian reserve of these patients. Therefore, we aimed to evaluate, the ovarian reserve and doppler characteristics of MS patients using immunomodulating drugs. MATERIAL AND METHODS: MS patients using immunomodulating drugs (interferon (IFN) ß and glatiramer acetate) and age-matched healthy controls were included in the study. Subjects were examined in the early follicular phase of the menstrual cycle with transvaginal ultrasound to evaluate ovarian volume, antral follicle count (AFC) and ovarian stromal artery Doppler. On the same day, blood was taken for determining serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels. A subgroup analysis was also carried out between MS patients using only IFN ß and controls to compare the same parameters. RESULTS: Mean ovarian volume and total AFC were lower in MS patients using immunomodulating drugs than in the controls. FSH and E2 levels did not show any differences between the groups, but LH levels were significantly higher in MS patients. All the Doppler parameters of the ovarian stromal artery were higher in MS patients but not significantly. In the subgroup analysis, the same significant differences were found for ovarian volume, AFC and LH levels. In addition, MS patients showed significantly higher mean pulsatility index measurement than the controls. CONCLUSION: The findings of this study demonstrated diminished ovarian volume and follicular reserve in MS patients using immunomodulating drugs compared to age matched healthy controls. However, further studies are required to elucidate whether compromised ovarian reserve in MS patients is due to drugs or the disease itself.

Diagnosis and management of vaginal mullerian cyst in a virgin patient.

Benign cystic lesions of the vagina are uncommon and may become symptomatic. We describe two symptomatic anterior vaginal wall cysts in a virgin patient and the usefulness of imaging modalities. A 36-year-old virgin woman presented with a complaint of vaginal bulging and pelvic pressure. Pelvic examination revealed a cystic mass protruding from the vagina surrounded by the intact hymen. The initial abdominopelvic ultrasound showed a hypoechoic cystic mass measuring 42 x 20 mm in the vagina. She then had a pelvic magnetic resonance imaging (MRI) that revealed two anterior vaginal wall cysts with no communication with the urethra or bladder. The cysts were excised and histologic examination with mucicarmine revealed mucin-secreting tall columnar cells consistent with a diagnosis of mullerian cyst. While both ultrasonographic examination and MRI are helpful in localizing vaginal cysts, MRI is superior in showing multiple cystic lesions of the vagina and their communication with the surrounding structures.

Outcome of vasectomies performed at a Turkish metropolitan maternity hospital.

OBJECTIVE: To determine prospectively the outcome of vasectomies performed by two trained surgeons over a 9-month period at the Ministry of Health Ankara Etlik Maternity and Women's Health Teaching and Research Hospital Family Planning Centre. METHODS: The demographic data, source of information concerning the method, sexual function before and after voluntary no-scalpel vasectomy, compliance with the post-vasectomy follow-up program of men applying for a vasectomy were analyzed. All patients were contacted by telephone and invited for follow-up visits for counseling, inquiry regarding sexual dysfunction, and performance of a semen analysis. RESULTS: The patients were married men, mostly primary school graduates, with more than one child. Sources of information were health services and/or health personnel for 89% of the patients. Of the 279 men who underwent a vasectomy and who were later contacted by phone, 131 (47%) came for a follow-up assessment. There was only one post-vasectomy pregnancy (0.8%). The incidence of reported sexual problems did not change after the procedure. Vasectomy did not affect the sexual function of men in our study. CONCLUSION: Compliance with follow-up after vasectomy, which is extremely important for assessment of its successful outcome, is low.

Efficiency of oocyte cryopreservation: a meta-analysis.

OBJECTIVE: To determine the efficiency of oocyte cryopreservation relative to IVF with unfrozen oocytes. DESIGN: Meta-analysis. SETTING: Academic assisted reproduction center. PATIENT(S): Results of all reports from January 1997 to June 2005 with the patients undergoing IVF-intracytoplasmic sperm injection (ICSI) with cryopreserved cycles between 1996 and 2004 were compared with those of patients who underwent IVF-ICSI with unfrozen oocytes in 2002 and 2003 in our program. INTERVENTION(S): Mean age and number of ET cycles originating from unfrozen oocytes was matched with those for thaw cycles originating from oocytes cryopreserved with a slow-freezing (SF) protocol. Vitrification (VF) reports were not included in the comparative analysis because of a small number of pregnancies (10) before June 2005. MAIN OUTCOME MEASURE(S): The comparison of fertilization rate, clinical pregnancy, and live-birth rates per injected oocyte, clinical pregnancy and live-birth rates per transfer, and implantation rate between IVF-ICSI cycles with frozen and unfrozen oocytes. RESULT(S): Live-birth rates per oocyte thawed were 1.9% and 2.0% for SF and VF, respectively, before June 2005. Live-birth rates per injected oocyte and ET, respectively, were 3.4% and 21.6% for SF and were 6.6% and 60.4% for IVF with unfrozen oocytes. Compared to women who underwent IVF after SF, IVF with unfrozen oocytes resulted in significantly better rates of fertilization (odds ratio [95% confidence interval]); 2.22 (1.80, 2.74), of live birth per injected oocyte; 1.5 (1.26, 1.79), and of implantation; 4.66 (3.93, 5.52). These odds ratios were lower when oocyte cryopreservation success rates from 2002-2004 were compared with those for IVF with unfrozen oocytes. When the reports after June 2005 were considered, this trend did not appear to continue. With the consideration of VF reports after June 2005, however, higher pregnancy rates were achieved. CONCLUSION(S): In vitro fertilization success rates with slow-frozen oocytes are significantly lower when compared with the case of IVF with unfrozen oocytes. Although oocyte cryopreservation with the SF method appears to be justified for preserving fertility when a medical indication exists, its value for elective applications remains to be determined. Pregnancy rates with VF appear to have improved, but further studies will be needed to determine the efficiency and safety of this technique.

Fertility and recurrence results of conservative surgery for borderline ovarian tumors.

OBJECTIVES: To evaluate the fertility and recurrence outcomes in women treated with fertility-sparing surgery for borderline ovarian tumors. METHODS: A total of 142 patients with borderline ovarian tumors managed surgically from 1993 to 2004 were identified from gynecologic oncology and pathology files of SSK Ankara Maternity and Women's Health Teaching Hospital. Sixty-two of those patients who had conservative surgery were eligible for the study. Information was acquired by retrospective medical record review and patient interview. RESULTS: The observed recurrence rates after radical and fertility-sparing surgery were 0.0% and 6.5%, respectively. Four patients from the conservative surgery group developed recurrence, in contrast to none of the patients from the non-conservative surgery group. No disease-related deaths occurred in any group. In the conservatively managed group, ten women had successful pregnancies, with a total of 10 live births and 3 abortions. The mean duration of follow-up for the conservative surgery group was 44.3 months (range, 3-128). CONCLUSION: Fertility-sparing surgery for borderline ovarian tumors should be considered for women in the reproductive age group who desire preservation of fertility. Recurrence is noted significantly more often after this type of treatment and close follow-up is needed to detect recurrent disease.

Chylous ascites following para-aortic lymphadenectomy: a case report.

BACKGROUND: Chylous ascites is an uncommon complication following para-aortic lymph node dissection in the management of gynecologic malignancies. Treatment options are serial paracentesis, medium-chain triglyceride diet, total parenteral nutrition and somatostatin as conservative management and peritoneovenous shunting, and surgical exploration for refractory cases. CASE: A 31-year-old female patient developed chylous ascites following para-aortic lymph node dissection for borderline mucinous tumor of the ovary. Conservative management options failed with recurrence of chylous ascites. Chylous ascites resolved after surgical closure of the lymphatic fistula on the cisterna chyli. There was no evidence of ascites at 10 months follow-up. CONCLUSION: If the patient is a good surgical candidate, surgical exploration should be considered earlier in the treatment of refractory chylous ascites.