Regular Menses Research Articles

MON-354 Undiagnosed Addison's Disease as a Cause of Infertility

Background: There are multiple potential mechanisms for infertility in AD (Addison’s disease) including suppression of HPG axis, LFOR (low functional ovarian reserve) secondary to AH (adrenal hypoandrogenism) or concomitant autoimmune POF (premature ovarian failure), as well as suppressive effect from high 17-OHP (17α-hydroxyprogesterone). Nonetheless, there is scarce literature concerning this complication of AD. Clinical Case: A 28 year old female with a normal BMI and a history of hypothyroidism, suspected PCOS, and spontaneous abortion presented to RE (Reproductive Endocrinology) for a 2 year history of primary infertility. She had menarche at age 12, with regular menses for 6 years until OCP was initiated. At age 24 she spontaneously conceived, but unfortunately miscarried. She subsequently developed oligomenorrhea, reporting menses every 3-4 months in the absence of hirsutism or acne. Initial evaluation demonstrated negative β-hCG, normal TSH 1.27 mcIU/ml (0.27-4.2), high anti-TPO antibodies 1040 IU/ml (<34), progesterone 12.79 ng/ml (0.06-0.89 follicular, 1.83-23.9 luteal), AMH 13.5 ng/ml (1.03-11.1), and 17-OHP 272 ng/dl (<80 follicular, <285 luteal), and low DHEA-S 20.6 mcg/dl (98.8-340) and free testosterone 1.6 pg/ml (0.16.4). AFC (antral follicle count) was 50, and semen analysis and HSG were unrevealing. Elevated 17-OHP was thought to represent luteal phase, but repeat in early follicular phase remained elevated, prompting referral to Endocrinology. Co-syntropin stimulation test was performed with pre-ACTH 17-OHP persistently elevated (546 ng/dl), with minimal increase 1 hour post-ACTH (598 ng/dl). Cortisol failed to stimulate increasing only from 11 to 14 mcg/dl post-ACTH. Further evaluation revealed elevated ACTH (324 pg/ml), and positive anti-adrenal antibodies. Following diagnosis of AD, HC (hydrocortisone) 10 mg in the morning and 2.5 mg in the afternoon was initiated with improvement in menstrual regularity to 34 day cycles. RE recommended initiation of letrozole for ovulation induction, and intrauterine insemination. However, given improvement in cycles with HC, Endocrinology recommended delaying fertility treatments temporarily. Four months after HC initiation, pregnancy was confirmed, and she subsequently delivered a healthy baby girl. Conclusion: This case emphasizes the importance of a thorough endocrinologic evaluation in patients with infertility, particularly those with other autoimmune endocrinopathies. The etiology of infertility in AD is likely multifactorial, and there is minimal supportive literature to date. While some authors have proposed LFOR secondary to adrenal hypoandrogenism or POF as an underlying etiology, this unique case describes a patient with high AMH and AFC, who had successful conception and pregnancy following initiation of HC replacement.

Abstract P1-11-06: Systematic evaluation of ovarian reserve in young breast cancer patients treated by sequential chemotherapy

Abstract Most women in reproductive age diagnosed with breast cancer receive (neo)adjuvant chemotherapy. Fertility preservation is part of the standard of care for these young women. Patients and methods We report preliminary results of a prospective multicentric cohort evaluating ovarian reserve during and after chemotherapy and fertility preservation in young (≤ 38 years old) in women aged ≤ 38 years, treated for a breast cancer with (neo)adjuvant anthracyclins and taxanes based chemotherapy, between July 2011 and December 2016. Fertility preservation was offered in patients (pts) who received adjuvant chemotherapy. The median duration of follow up was 2,6 years (4 months-5,3 years). The aim of this study was to evaluate the ovarian reserve assessed by antimullerian hormone and antral follicular count. The incidence of amenorrhea (defined by absence of menses ≥ 3 months), ovarian failure (absence of menses ≥ 12 months), chemotherapy induced menopause (absence of menses ≥ 24 months) was collected. Results One hundred and thirty-two pts were included in 10 centers. Data are available for 127 pts. For 4 pts, the scheduled chemotherapy was not received. One pt withdrew her consent. Chemotherapy was neoadjuvant for 43 pts and adjuvant for the 84 others. Fifty-eight asked for fertility preservation and received ovarian stimulation (all in adjuvant setting). Median age was 32 years (23-37). Eighty pts had a previous pregnancy. Three of them remained nulliparous. Among the 77 others, 36 had 1 child, 31 had 2 children and 10 pts 3 or more children respectively. At the time of diagnosis, 90% had regular menses and 75% had a contraception. The median initial antral follicular count was 21.5 (Min 1- Max 100). The AMH level significantly decreased during chemotherapy with no secondary return to baseline value over the first 9 months after end of treatment: median of 20.9 pmol/l (0.5-223) before chemotherapy, 12,8 (0,5-120) at the second cycle of chemotherapy (C2), 3 (0,5-20) at C4, 0,5 (0,5-4,4) at C6, 0,5 (0,5-25,1) 3 months after the end of chemotherapy (M3), 0,6 (0,5-29) at M6, and 3 (0,5-29,8) at M9. At last follow-up, 46% of pts experienced amenorrhea, 7% an ovarian failure and 3% a chemo-induced menopause. The highest incidence of amenorrhea (61%) was at M3. At M12, 7% of pts remained amenorrhoeic. The AMH initial level was not significantly lower in pts who experienced amenorrhea compared to those who did not (25.5 versus 35.1, p = 0,087). Ovarian stimulation and BRCA status did not impact risk of amenorrhea. At 2 years, overall survival rate was 96% and progression free survival rate was 90% (6 deaths and 18 progression events). Conclusion (Neo)adjuvant sequential breast cancer chemotherapy is associated with a decrease of AMH level and amenorrhea. Our results suggest a significant risk of premature ovarian failure. Fertility preservation has to be proposed to these young patients. Citation Format: Mailliez A, Pigny P, Bogart E, Diomande S, Jeazet Tiotsia H, Bonneterre J, Le Deley MC, Decanter C. Systematic evaluation of ovarian reserve in young breast cancer patients treated by sequential chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-06.

Congenital adrenal hyperplasia with maple syrup urine disease: An example of consanguinity impact.

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolically inherited disorder, caused by an abnormal function of the branched-chain α-keto acid dehydrogenase complex in the mitochondria. Case Presentation: The proband was born after a full-term pregnancy and normal vaginal delivery, with a good Apgar score (8, 9 at 1 and 5 minutes) and the birth weight of 2.5 kg with ambiguous genitalia in the form of phallus-like structure (3 cm), the fusion of labio-scrotal folds and urogenital sinus. The third day after birth, the proband was lethargic and developed hyperkalemia and hyponatremia, which required intravenous fluid therapy and hormonal replacement with hydrocortisone and fludrocortisone. The treatment was based on the positive family history of congenital adrenal hyperplasia in an older male sibling. Laboratory tests, cytogenetic study, tandem mass spectroscopy, and surgery were performed for the affected individual (II-8) using standard procedures. The laboratory and the treatment revealed significant improvements. Follow-up tandem mass spectroscopy results were observed in the normal range. The affected individual was treated with prednisone (2.5 mg bid) and Florinef (Fludrocortisone) (0.1 mg OD). The subject had regular menses, while acne and hirsutism were not observed. Conclusion: We are reporting the first case of MSUD associated with CAH, 21-hydroxylase deficiency salt-losing type and suggest that glucocorticoids might have an important role in treating MSUD cases.

Markers of lipid and protein peroxidation among Nigerian university students with dysmenorrhea.

Oxidative stress has been associated with primary dysmenorrhea, but studies that have assessed multiple markers of peroxidation are scarce. This study investigated malondialdehyde (MDA), nitrotyrosine (3-NT), and protein carbonyls (PrCarb) as markers of oxidative stress and antioxidant status by serum alpha tocopherol level in young Nigerian women with dysmenorrhea. In a case-control design, 45 female undergraduates who had had regular menses for at least six previous cycles were recruited consecutively from a university clinic as cases and 45 apparently healthy age-matched counterparts in their hall of residences as controls. Serum levels of MDA, 3-NT, and PrCarb were determined using standard methods, and the values were compared between cases and controls using Mann-Whitney U-test and graphs. Study participants' ages range from 16 to 29 years (mean = 22.0 ± 3.1 years). Serum level of 3-NT (45.89 ± 37.11 vs 21.27 ± 13.94 ng/mL) and MDA (0.75 ± 0.19 vs 0.45 ± 0.11 nmol/mL) was significantly higher in cases than controls. Plasma alpha tocopherol was significantly lower in cases (7.51 ± 1.95 μmol/L) than controls (8.98 ± 1.95 μmol/L). Conversely, PrCarb levels were not significantly difference between cases and controls. There were significant correlations between alpha tocopherol and 3-NT (r = -0.285; P = 0.007) and MDA (r = -0.321; P = 0.002), whereas this relationship was not shown with PrCarb (r = -0.073; P = 0.496). Remarkable lipid and protein peroxidation observed in young Nigerian women with dysmenorrhea was accompanied by correspondingly low level of serum alpha tocopherol suggesting potential need for vitamin E supplementation.

Use of clomiphene citrate alone, urinary follicle-stimulating hormone alone, or both combined sequentially in patients with unexplained subfertility undergoing intrauterine insemination: A randomized trial.

Objective:To compare the successes of clomiphene citrate (CC) alone, pure human urinary follicle-stimulating hormone (uFSH) alone, and both combined sequentially in patients with unexplained subfertility couples undergoing intrauterine insemination (IUI).Materials and Methods:Patients aged 18-38 years who had a normal uterine cavity, at least one normal fallopian tube, and regular menses and were unable to conceive despite unprotected intercourse for at least 12 months were randomized to receive CC alone, uFSH alone, or sequential CC and uFSH before a single IUI. The primary outcomes were clinical pregnancy and live birth rates. The study was approved by the ethics committee of our institution.Results:A total of 135 patients were randomized, and 121 of these were able to complete the study. Of these, 30% (n=36) had CC alone, 34% (n=41) had uFSH alone, and 36% (n=44) had sequential CC and uFSH. The three groups did not significantly differ in terms of age, duration of infertility, hormone levels, and semen parameters. For CC alone, uFSH alone, and sequential CC plus uFSH groups, pregnancy rates were 8.3%, 17.1%, and 18.2%, respectively (p>0.05), and live birth rates were 8.3%, 12.1%, and 13.6%, respectively (p>0.05).Conclusion:In women with unexplained infertility, use of uFSH seemed to increase the success rate compared with CC alone. The sequential regime can significantly reduce the treatment cost if gonadotropin/IUI cycles are planned.

Fragile X Associated Primary Ovarian Insufficiency (FXPOI): Case Report and Literature Review.

Abnormalities in the X-linked FMR1 gene are associated with a constellation of disorders, which have broad and profound implications for the person first diagnosed, and extended family members of all ages. The rare and pleiotropic nature of the associated disorders, both common and not, place great burdens on (1) the affected families, (2) their care providers and clinicians, and (3) investigators striving to conduct research on the conditions. Fragile X syndrome, occurring more severely in males, is the leading genetic cause of intellectual disability. Fragile X associated tremor and ataxia syndrome (FXTAS) is a neurodegenerative disorder seen more often in older men. Fragile X associated primary ovarian insufficiency (FXPOI) is a chronic disorder characterized by oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. There may be significant morbidity due to: (1) depression and anxiety related to the loss of reproductive hormones and infertility; (2) reduced bone mineral density; and (3) increased risk of cardiovascular disease related to estrogen deficiency. Here we report the case of a young woman who never established regular menses and yet experienced a 5-year diagnostic odyssey before establishing a diagnosis of FXPOI despite a known family history of fragile X syndrome and early menopause. Also, despite having clearly documented FXPOI the woman conceived spontaneously and delivered two healthy children. We review the pathophysiology and management of FXPOI. As a rare disease, the diagnosis of FXPOI presents special challenges. Connecting patients and community health providers with investigators who have the requisite knowledge and expertise about the FMR1 gene and FXPOI would facilitate both patient care and research. There is a need for an international natural history study on FXPOI. The effort should be coordinated by a global virtual center, which takes full advantage of mobile device communication systems.

Bleeding, cramping, and satisfaction among new copper IUD users: A prospective study

ObjectiveWe assess change in bleeding, cramping, and IUD satisfaction among new copper (Cu) IUD users during the first six months of use, and evaluate the impact of bleeding and cramping on method satisfaction.MethodsWe recruited 77 women ages 18–45 for this prospective longitudinal observational cohort study. Eligible women reported regular menses, had no exposure to hormonal contraception in the last three months, and desired a Cu IUD for contraception. We collected data prospectively for 180 days following IUD insertion. Monthly, participants reported bleeding scores using the validated pictorial blood loss assessment chart (PBAC), IUD satisfaction using a five-point Likert scale, and cramping using a six-level ordinal scale. We used multiple imputation to address nonrandom attrition. Structural equation models for count and ordered outcomes were used to model bleeding, cramping, and IUD satisfaction growth curves over the six monthly repeated assessments.ResultsBleeding significantly decreased (approximately 23%) over the course of the study from an estimated PBAC = 195 at one month post-insertion to PBAC = 151 at six months (t = -2.38, p<0.05). Additionally, IUD satisfaction improved over time (t = 2.65, p<0.01), increasing from between “Neutral” and “Satisfied” to “Satisfied” over the six month study. Cramping decreased notably over the six month study from between biweekly and weekly, to once or twice a month (t = -4.38, p<0.001). Finally, bleeding, but not cramping, was associated with IUD satisfaction across the study (t = -2.31, p<0.05) and at study end (t = -2.81, p<0.01).ConclusionsNew Cu IUD users reported decreasing bleeding and cramping, and increasing IUD satisfaction, over the first six months. Method satisfaction was negatively associated with bleeding.

How reliable are regular menses as a guide to endocrine health?

How reliable are regular menses as a guide to endocrine health?

Does anti-Müllerian hormone predict change in menopausal symptoms following risk-reducing salpingo-oophorectomy? A prospective observational study

Objectives: The aim of this study was to investigate whether serum anti-Müllerian hormone (AMH) predicts symptom burden after risk-reducing salpingo-oophorectomy (RRSO) in order to individualize counseling.Methods: Patient-reported menopausal symptoms, sexual functioning, and psychological distress (depression and anxiety) were assessed 1 day before (T0) and 6 weeks (T1) and 7 months (T2) after RRSO. AMH was assessed before RRSO. Multivariable regression analysis was used to investigate the association between AMH and short-term and long-term change in symptom burden following RRSO.Results: Ninety-one premenopausal women at high risk of ovarian cancer were included. Presurgical AMH was not related significantly to change in symptoms post RRSO. As a secondary outcome we found that regular menses before RRSO was associated specifically with long-term increase in hot flushes (sr = 0.40, p = 0.001; total R2 = 0.171) and depression (sr = 0.29, p = 0.012; total R2 = 0.132). Earlier receipt of chemotherapy was associated with long-term improvement in sexual functioning (sr = 0.24, p = 0.041; total R2 = 0.348).Conclusion: In this cohort, AMH was not a significant predictor of change in symptoms following RRSO. Regular menses prior to RRSO and earlier receipt of chemotherapy were significantly, but relatively weakly, associated with changes in outcomes 6 weeks and/or 7 months after RRSO.

Trust in Physicians and Medical Experience Beliefs Differ Between Women With and Without Polycystic Ovary Syndrome.

ContextWomen with polycystic ovary syndrome (PCOS) report dissatisfaction with their early medical care. Little is understood about factors that can encourage stronger patient-provider relationships and promote treatment adherence.ObjectiveTo compare trust in physicians and beliefs about social support from health care providers between women with and without PCOS.DesignCross-sectional study with online questionnaire.SettingMedical clinic referral or broader community recruitment via advertising and websites.ParticipantsThree hundred thirty-two US-based women with PCOS or with regular menses (n = 134 and n = 198, respectively).Main Outcome MeasuresTrust and social support toward health care providers [primary care physicians (PCPs), specialists, and/or nurse practitioners and physician assistants].ResultsPCOS was associated with greater distrust in the PCP’s opinion (P < 0.01) and greater confidence about the PCP’s prioritization of general health concerns (P = 0.04) than the comparison group. Patients with PCOS felt that the PCP spent less effort and were less qualified to treat PCOS health concerns than general health concerns (both P < 0.001). No significant associations were observed between PCOS diagnosis and trust in specialists. When examining social support, women with PCOS felt they had more arguments with their health care providers than the comparison group (P = 0.02).ConclusionWomen with PCOS reported greater overall distrust in the PCP’s opinions and more arguments with their health care providers than women without PCOS. These findings support a need to identify additional areas of improvement in the patient-provider relationship to ensure continuity of care for patients with PCOS who require life-long surveillance.

Early medical abortion with self-administered low-dose mifepristone in combination with misoprostol.

AimThe aim of the present study was to investigate the safety and efficacy of low‐dose mifepristone combined with self‐administered misoprostol for termination of early pregnancy.MethodsA total of 533 women seeking medical abortion in early pregnancy (≤49 days since the last menstrual period) were divided randomly into hospital‐ (H‐Mis, 250) and self‐ (S‐Mis, 283) administered misoprostol groups. Women in two groups took 100 mg of oral mifepristone in hospital followed by 200 μg of sublingual misoprostol 24 h later in hospital or home. The primary outcome parameter was complete abortion without surgical intervention. Secondary outcomes were uterine bleeding, return of regular menses, side effects and patient acceptability.ResultsHigh rates of complete abortion were observed for both the H‐Mis group (243/250; 94.8%) and the S‐Mis group (266/283; 94.0%). No significant differences in outcomes (complete abortion/failure rates) or side effects were observed between the two groups. General satisfaction rates were similar for the two groups (H‐Mis, 231/250, 92.4%; S‐Mis, 263/283, 92.9%; P > 0.05). Higher convenience of administration (H‐Mis, 211/250, 84.4%; S‐Mis, 270/283, 95.4%; P < 0.05) and privacy protection (H‐Mis, 214/250, 85.6%; S‐Mis, 267/283, 94.3%; P < 0.05) satisfaction rates were obtained for the S‐Mis group than for the H‐Mis group.ConclusionSelf‐administered sublingual misoprostol is as safe and effective as hospital‐administered misoprostol following low‐dose mifepristone to terminate early pregnancy (≤49 days of amenorrhoea) with fewer side effects.

Premature ovarian insufficiency and early depletion of the ovarian reserve in the monogenic Mulibrey nanism disorder.

What is the timing of onset and clinical course of premature ovarian insufficiency (POI) in patients with Mulibrey nanism (MUL), a monogenic disorder caused by mutations of the peroxisomal TRIM37 gene? The number of ovarian follicles is highly reduced already in infant and young MUL girls and the majority of them will have early depletion of follicles resulting in clinical and biochemical signs of POI. Both female and male patients with MUL show failure of sexual maturation, signs of hypogonadism and infertility. We studied the gonadal function, pubertal development and ovarian reserve in 33 MUL patients aged 5.1-47.3 years (median age 22.3) at the end of observation. The patients were followed between 2004 and 2014 and 19 pubertal or postpubertal patients were enrolled in a cross-sectional study. The period of postnatal activation of the hypothalamic-pituitary-gonadal axis (minipuberty), pubertal development and menstrual history were assessed longitudinally. The cross-sectional study included gynecological examination, analysis of reproductive hormones and ultrasonography with evaluation of ovarian volume and antral follicle count. Infant girls experienced a transient minipuberty with a high FSH surge. In childhood, gonadotropins were normal or slightly elevated but began to rise to hypergonadotropic levels in prepuberty. Anti-Müllerian hormone (AMH) levels remained undetectable or low throughout childhood. The onset of puberty occurred spontaneously and the median age at menarche was 12.5 years. Of the patients, 54% never attained regular menses and 10 years from menarche, only 8% of the women menstruated regularly. In the cross-sectional study, none of the patients had normal ovarian morphology under ultrasonography. Ovaries were hypoplastic and 82% had no or fewer than two visible antral follicles. AMH levels were undetectable in the vast majority (89%). The Finnish MUL patients genotypically form a homogenous group and therefore it is possible, that different TRIM37 mutations lead to different hypogonadal phenotypes. However, to date there is no known genotype-phenotype correlation in MUL. In MUL, AMH is a useful marker of ovarian function. MUL should be added to the list of syndromes associated with POI and correspondingly, TRIM37 should be added to the list of genes associated with POI. To our knowledge, TRIM37 is the first known gene coding for a peroxisomal membrane protein associated with female gonadal failure and infertility. Elucidating the role of syndromic genes in reproduction may aid in a greater understanding of ovarian biology. This study was supported by the Finnish Foundation for Pediatric Research, Finska Läkaresällskapet, the Sigrid Jusélius Foundation and Helsinki University Hospital Research Funds. The authors declare no conflicts of interest. Not applicable.

Uterine transposition after radical trachelectomy

To report the first uterine transposition for fertility sparing in cervical cancer. We report a 33-year-old woman with stage Ib1 cervical cancer (b2 cm in size) who had a radical trachelectomy that, after the definitive pathological report, fulfilled the criteria for adjuvant radiotherapy. The patient had eggs retrieval and received gosereline 10.8 mg before surgery. The uterine corpus and ovaries were detached from the previous vaginal anastomosis, laparoscopically mobilized, and sutured in the right upper abdominal wall with non-absorbable transparietal suture. The adjuvant external beam radiotherapy (45 Gy) was delivered in the pelvis. One week after, the uterus and ovaries were repositioned and sutured in the vagina. The patient had hospital discharged in the 2° post-operative day and no early complications. After 6 months of follow-up the patient has regular menses and no evidence of recurrence. Uterine transposition is feasible after radical trachelectomy in selected patients who still desire to preserve fertility. However, further studies that address its effectiveness and safety are required.

Menstrual Dysfunction in Girls From the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study.

Little is known about reproductive function in girls with youth-onset type 2 diabetes. To characterize girls with irregular menses and effects of glycemic treatments on menses and sex steroids in the Treatment Options for Type 2 Diabetes in Youth (TODAY) study. Differences in demographic, metabolic, and hormonal characteristics between regular- vs irregular-menses groups were tested; treatment group (metformin with or without rosiglitazone, metformin plus lifestyle) effect on menses and sex steroids over time in the study was assessed. This is a secondary analysis of TODAY data. Multicenter study in an academic setting. TODAY girls not receiving hormonal contraception and those at least 1-year postmenarche were included. Irregular menses was defined as three or fewer periods in the prior 6 months. Of eligible participants with serum measurement of sex steroids (n = 190; mean age, 14 years), 21% had irregular menses. Those with irregular vs regular menses had higher body mass index (BMI) (P = 0.001), aspartate aminotransferase (AST) (P = 0.001), free androgen index (P = 0.0003), and total testosterone (P = 0.01) and lower sex hormone-binding globulin (SHBG) (P = 0.004) and estradiol (P = 0.01). Differences remained after adjustment for BMI. There was no treatment group effect on menses or sex steroids at 12 or 24 months, and no association of sex steroids was seen with measures of insulin sensitivity or secretion. Menstrual dysfunction is common in girls with recently diagnosed type 2 diabetes and associated with alterations in sex steroids, SHBG, and AST but not with alteration in insulin sensitivity or β-cell function and did not improve with 2 years of antihyperglycemic treatment.

Extra Uterine Choriocarcinoma Mimicking as Ectopic Pregnancy: A Rare Case Report

Choriocarcinomas are germ cell tumours formed by trophoblastic elements (Mundkur et al., J Clin Diagn Res 9(1):QD01–2; 2015). Gestational choriocarcinoma can occur after molar pregnancy, tubal pregnancy or antecedent normal pregnancy. Primary extra-uterine choriocarcinoma is very rare. We report here a case of broad ligament choriocarcinoma who presented with a complaint of pain in lower abdomen off and on. She had a history of dilation and evacuation for spontaneous abortion 3 months back and then she had regular menses. Her transvaginal sonography revealed 42 x 35 mm size right adnexal mass which was more consistent with ectopic pregnancy and her serum human chorionic gonadotropin (β-Hcg) level was 1,76,075 mIU/ ml. Finally, patient was diagnosed as ruptured tubal ectopic pregnancy and thus, she underwent laparotomy. On laparotomy, there was purple colored broad ligament mass of size 5x6 cm with highly increased vascularity in right side which was removed with difficulty and massive bleeding occurred. So, total abdominal hysterectomy was done. Histopathological report showed choriocarcinoma of right broad ligament invading myometrium. The patient was given 6 cycles of EMACO regime. Serum β-Hcg levels of the patient gradually declined and eventually became negative after 2 weeks of 5th EMACO. With this case report, we aim to emphasize that while diagnosing the ectopic pregnancy, even very rare, the tubal choriocarcinoma should be kept in mind. We report a case of primary extra-uterine choriocarcinoma that was mistaken for an ectopic pregnancy.

Anti-Müllerian hormone in pre-menopausal females after ablative radioiodine treatment for differentiated thyroid cancer.

In recent years, anti-Mullerian hormone (AMH) has been considered a reliable index of ovarian reserve. There are few data on AMH values in thyroid cancer. The aim of this study was to evaluate AMH levels in pre-menopausal women with a history of low-risk thyroid cancer. Thirty-four women (aged 40.7 ± 6.7 years) were studied 7.1 ± 0.9 years after surgery and at least one RAI treatment. A group of 23 thyroid cancer women (41.6 ± 7.4 years) who had undergone only thyroidectomy served as controls. AMH, follicle-stimulating hormone (FSH) and estradiol were assayed on days 2-3, and prolactin and progesterone levels on days 21-24 of the menstrual cycle. Pregnancy (RAI group 62%; control group 61%) and miscarriage rates (18% and 26%) were similar. AMH levels were similar in the RAI (10.7 ± 1.7 pmol/l) and control (17.5 ± 4.7 pmol/l) groups. Regular menses were reported in 41% and 52% of RAI and control subjects, respectively. Non-ovulatory cycles were noted in 26% and 35% of RAI and control women, respectively. AMH levels were found to be negatively correlated with age (RAI group P = 0.0003; control group P = 0.0001) and FSH, and positively correlated with progesterone, but not with the other hormonal parameters. AMH should replace FSH in the evaluation of gonadal reserve in pre-menopausal thyroid cancer women. At present, age is the only predictor of AMH levels. About one out of two women with a history of thyroid cancer suffers from menstrual dysregulation, but infertility must be considered a low risk.

Abnormal Uterine Bleeding in Women in Child Bearing Period of Arar City, Northern Saudi Arabia

Background: Abnormal uterine bleeding (AUB) affects as many as one-third of reproductive-aged women. Women with AUB may experience pain, embarrassment and inconvenience that can have a significant impact on their lives. This study was carried out aiming to assess the pattern and possible causes of abnormal uterine bleeding in reproductive aged women in Arar city, Northern Saudi Arabia. Methods: The study was conducted at Maternal and Child Hospital of Arar City, during the period from 1/5/2017 to 30/7/2017. Data collected by personal interview with cases and filling a pre-designed online questionnaire. Collected data was coded and analyzed using statistical package for the social sciences (SPSS, version 16). Descriptive statistics for the quantitative and qualitative variables were used. Results: In our study 100 women were included, with mean age 30.5±6.9, mean age of menarche was 13.1 (±1.8) and 52% of them had regular menses. Pattern of bleeding was menorrhagia in 52%. The cause of bleeding was dysfunctional uterine bleeding in 59% of cases, Intrauterine device complications in14%, Uterine fibroid in 12% of cases and contraceptive pills complications in 15%. Only 13% of them treated surgically while 87.0% treated medically. Conclusion: The most common cause of abnormal uterine bleeding was endometrial hyperplasia (in 59%), and the contraceptive pills complications comes in the second place (in 15%), then the Intrauterine device complications (in 14%) and the uterine fibroid (in 12%). Health education sittings is recommended to increase the public awareness about the causes and importance of seeking medical care during AUB attacks specially in premenopausal period.

Epigenetic Aberration of FMR1 Gene in Infertile Women with Diminished Ovarian Reserve.

Objective The diminished ovarian reserve (DOR) is a condition characterized by a reduction in the number and/or quality of oocytes. This primary infertility disorder is usually accompanied with an increase in the follicle-stimulating hormone (FSH) levels and regular menses. Although there are many factors contributing to the DOR situation, it is likely that many of idiopathic cases have genetic/epigenetic bases. The association between the FMR1 premutation (50-200 CGG repeats) and the premature ovarian failure (POF) suggests that epigenetic disorders of FMR1 can act as a risk factor for the DOR as well. The aim of this study was to analyze the mRNA expression and epigenetic alteration (histone acetylation/methylation) of the FMR1 gene in blood and granulosa cells of 20 infertile women. Materials and Methods In this case-control study, we analyzed the mRNA expression and epigenetic altration of the FMR1 gene in blood and granulosa cells of 20 infertile women. These women were referred to the Royan Institute, having been clinically diagnosed as DOR patients. Our control group consisted of 20 women with normal antral follicle numbers and serum FSH level. All these women had normal karyotype and no history of genetic disorders. The number of CGG triplet repeats in the exon 1 of the FMR1 gene was analyzed in all samples. Results Results clearly demonstrated significantly higher expression of the FMR1 gene in blood and granulosa cells of the DOR patients with the FMR1 premutation compared to the control group. In addition, epigenetic marks of histone 3 lysine 9 acetylation (H3K9ac) and di-metylation (H3K9me2) showed significantly higher incorporations in the regulatory regions of the FMR1 gene, including the promoter and the exon 1, whereas tri-metylation (H3K9me3) mark showed no significant difference between two groups. ConclusionOur data demonstrates, for the first time, the dynamicity of gene expression and histone modification pattern in regulation of FMR1 gene, and implies the key role played by epigenetics in the development of the ovarian function.

Risk factors associated with secondary infertility in women of childbearing age: A matched case–control study

Background: Childbearing and rearing are important events in every human life and are associated with the feeling of completeness, family integration, and happiness. However, approximately 1 in 10 couples worldwide experience difficulty in achieving conception. Objective: This study aims to determine the risk factors associated with secondary infertility in women attending the obstetrics and gynecology clinics of a tertiary hospital in Lagos, Nigeria. Methodology: This individually matched case–control study was carried out from July to October 2015. A total of 160 cases were recruited from the gynecology clinic and 160 matched controls were recruited from the antenatal clinic. Data were collected using a structured interviewer-administered questionnaire. The information collected included sociodemographic characteristics, social history, and obstetric and gynecological history. A conditional logistic regression analysis controlling for possible confounders, which included variables significant at the univariate level, was undertaken. Results: Association with secondary infertility was found with a history of unsafe abortion (adjusted odds ratio [AOR] = 9.3607, confidence interval [CI] = 3.7664–23.2645), alcohol use (AOR = 16.8102, CI = 1.3972–202.2487), family history of secondary infertility (AOR = 4.7346, CI = 1.4892–15.0523), and history of sexually transmitted infections (AOR = 4.5428, CI = 1.7658–11.6866). Contrariwise, a history of regular menses and normal vaginal delivery, respectively, were found to be protective. No statistically significant relationship was observed between educational level or alcohol use of partners and secondary infertility in this study. Conclusion: The extrinsic risk factors identified in this study should be taken into consideration when designing preventive and treatment programs toward reducing the burden of secondary infertility.

A Rare Cause of Pelvic Pain in a Teenage Girl

History of present illness: A 14-year-old female presented with rectal pain, pelvic pressure, urinary hesitancy and difficulty defecating despite daily laxative use. She had a history of irregular periods and was currently menstruating. Her vital signs were normal. Her abdominal exam was unremarkable and the external genitourinary exam showed a visible vaginal introitus and no masses. Significant findings: Due to pain out of proportion to her exam, an ultrasound of her pelvis was obtained and showed a blood-filled distended uterus, or hematometrocolpos (white arrow), with a 4.9 cm right ovarian cyst (blue arrow). A pelvic magnetic resonance imaging (MRI) then revealed an obstructed right hemi-vagina, normal left uterus and vagina and ipsilateral renal agenesis (red arrow) with normal left kidney (double arrow) consistent with obstructed hemivagina, ipsilateral renal agenesis (OHVIRA) syndrome. The patient underwent surgical repair with complete resolution of symptoms.Discussion: OHVIRA is rare syndrome that occurs due to a failure of lateral fusion of the Mullerian ducts.1 It affects an estimated 0.1%-3.8% of the population.2 The majority of these cases are associated with ipsilateral renal anomalies, but up to half can have contralateral anomalies.1,2 The most common presenting symptom is pelvic pain.1 On physical exam, patients may have a bulge in the vaginal wall which represents hematometrocolpos due to obstruction of outflow of menstrual blood. Transabdominal pelvic ultrasound or MRI are helpful modalities for diagnosis in adolescents.1,3 In one pediatric case series of OHVIRA, all 8 patients had a history of normal menses and presented with acute or chronic pelvic pain that began after menarche.2 All patients in this case series were initially misdiagnosed, due to the rarity of the disorder and the fact that most patients have a history of regular menses despite progressive pelvic pain. Definitive treatment requires surgical excision of the vaginal septum. Post-surgical prognosis is typically good;4-6 potential complications include endometriosis and increased risk for preterm labor or malpresentation.7 Topics: Pelvic pain, obstructed hemivagina, renal agenesis, rectal pain, hematometrocolpos, hematocolpos.