Elevated Follicle-stimulating Hormone Levels Research Articles

ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure

Primary ovarian insufficiency (POI) is a frequent disorder that affects ~1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone (FSH), leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene variants, most cases remain idiopathic. The aim of the present study was to identify and validate functionally new sequence variants in ATG (autophagy-related genes) leading to POI. We have reanalyzed, in silico, the exome sequencing data from a previously reported work performed in 69 unrelated POI women. Functional experiments using a classical hallmark of autophagy, the microtubule-associated protein 1 light chain 3β (LC3), were then used to link these genes to this lysosomal degradation pathway. We venture a functional link between ATG7 and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a decrease in autophagosome biosynthesis and consequently to an impairment of autophagy, a key biological process implicated in the preservation of the primordial follicles forming the ovarian reserve. Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI.

Clinical and genetic analysis in males with 46,XX disorders of sex development: A reproductive centre experience of 144 cases.

To explore the clinical features and assisted reproductive technology (ART) outcomes of 46,XX disorders of sex development (DSD) males, 144 males with 46,XX DSD were recruited in this retrospective study. The baseline information, clinical characteristics and ART outcomes of the participants were collected and analysed. The mean age was 29.06±4.50years. The mean volumes (95% CI) of left and right testicles were 2.16 (1.82-2.49) ml and 2.16 (1.83-2.49) ml, respectively. Cryptorchidism and/or hypospadias appeared in 19 patients (13.19%). Elevated levels of follicle-stimulating hormone (FSH) were found in 136 patients (95.10%) and increased luteinising hormone (LH) values were detected in 125 patients (92.59%). Eighty subjects (62.99%) had low testosterone values. Among 86 patients with status of sex-determining region Y (SRY)-gene and azoospermia factor (AZF) region available, fifteen (17.44%) patients were SRY-negative and AZF region was absent in every patient without exception. Additionally, fertility achieved in 87 patients through ART using donor spermatozoa. In conclusion, hypergonadotropic hypogonadism appeared as the main presentation of 46,XX DSD males regardless of the SRY status. The available fertility option proved to achieve live birth was limited to ART using donor spermatozoa.

A comparative study on ABO blood group and fertility hormones in infertile women in Calabar, Southern Nigeria

Infertility, a disorder of the reproductive system, is commonly linked to hormonal, pituitary, cervical, uterine, immunological or psychological factors. Besides these factors, it can also be idiopathic or unexplained. Hence, there is a need for more research to unravel the causes of the unexplained infertility. This work aimed at finding out whether there is any relationship between ABO blood group system and female infertility. The study design was cross-sectional. Three hundred women between 18 and 40 years attending fertility clinic at the University of Calabar Teaching Hospital, Calabar between 2011 and 2012 were recruited for this study. Serum progesterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were determined using Enzyme linked immunosorbent assay (ELISA) while ABO blood grouping was determined using the tube method. Statistical analysis was done using SPSS version 18. The confidence level was set at 95% where p-value less than 0.05 was considered statistically significant. The mean age of the women was 30.65 ± 5.47 years and the percentage distributions of the blood groups among the women were as follows: 24% A, 12% B, 4% AB and 60% O. The mean FSH levels of blood groups A and O individuals were significantly higher (p<0.05) than that of groups B. However, there was no significant difference (p>0.05) in the mean levels of progesterone, prolactin, LH and estradiol in the respective groups. From this study, 38% of the population had increased levels of progesterone, 58% and 18.7% had elevated prolactin and FSH levels respectively while 11.33% and 43.3% had reduced levels of LH and estradiol levels respectively. Though, there was high prevalence of hyperprolactinemia observed in this study, there was no strong association between ABO blood group and female infertility but, the increased FSH levels observed in blood groups A and O may be a potential link between blood group and infertility and therefore may be beneficial for further study.

Age-Specific IVF Outcomes in Infertile Women With Baseline FSH Levels ≥20 mIU/mL.

Infertile women with severely diminished ovarian reserve who have low birth chances with in vitro fertilization (IVF) are often denied treatment with autologous oocytes. This study was designed to determine age-specific treatment efficacy and clinical characteristics of infertile women with severely diminished ovarian reserve who had live birth following IVF with autologous oocytes. This retrospective cohort study investigated 291 infertile women who underwent 482 IVF cycles with autologous oocytes during 2004 to 2016 at our academically affiliated private fertility center. All women were aged <45 years and had maximum baseline follicle-stimulating hormone (FSH) levels ≥20 mIU/mL. Main outcome measures included pregnancy, spontaneous abortion, and live birth rates. Patient and treatment characteristics were compared for women who achieved a live birth to those who did not. Live birth rates were 8.6% per treated woman and 6% per started IVF cycle. The spontaneous abortion risk was 27% per clinical pregnancy. Age-specific live birth rates were highest at 17.2% for women <35 years and lowest at 1.9% for women >42 years. Women who achieved live birth were younger than those who did not (38.0 ± 8.0 vs 40.0 ± 6.0; P = .008), had lower FSH levels (25.0 ± 20.0 vs 32.5 ± 31.0; P = .006), and produced more oocytes (3.0 ± 5.0 vs 1.0 ± 2.0; P < .001), as well as transferrable embryos (2.0 ± 2.0 vs 0.0 ± 1.0; P < .001). Infertile women up to 45 years with severely diminished ovarian reserve achieve better live birth rates than previously reported and should not be denied access to IVF based on elevated FSH levels alone.

STX2 is a causative gene for nonobstructive azoospermia.

STX2 encodes a sulfoglycolipid transporter. Although Stx2 nullizygosity is known to cause spermatogenic failure in mice, STX2 mutations have not been identified in humans. Here, we performed STX2 mutation analysis for 131 Japanese men clinically diagnosed with nonobstructive azoospermia. As a result, we identified a homozygous frameshift mutation [c.8_12delACCGG, p.(Asp3Alafs*8)] in one patient. The mutation-positive patient exhibited loss-of-heterozygosity for 58.4 Mb genomic regions involving STX2, suggesting possible parental consanguinity. The patient showed azoospermia, relatively small testes, and a mildly elevated follicle stimulating hormone level, but no additional clinical features. Testicular histology of the patient showed universal maturation arrest and multinucleated spermatocytes, which have also been observed in mice lacking Stx2. PCR-based cDNA screening revealed wildtype STX2 expression in various tissues including the testis. Our results indicate that STX2 nullizygosity results in nonsyndromic maturation arrest with multinucleated spermatocytes, and accounts for a small fraction of cases with nonobstructive azoospermia.

Female Offspring From Chronic Hyperandrogenemic Dams Exhibit Delayed Puberty and Impaired Ovarian Reserve.

Female offspring of many species exposed to high doses of androgens in utero experience endocrine dysfunction during adulthood. The phenotype of offspring from females with prepregnancy hyperandrogenemia and impaired ovulation, however, has not been examined. We developed a mouse model of hyperandrogenemia by implanting a low-dose dihydrotestosterone (DHT) pellet 15 days before conception. Female offspring born to dams with hyperandrogenemia (DHT daughters) had delayed puberty (P < 0.05) with first estrus on postnatal day (PND) 41 compared with daughters from dams with physiological levels of DHT (non-DHT daughters, PND37.5). Serum follicle-stimulating hormone (FSH) levels in the DHT daughters were fourfold higher (P < 0.05) on PND21, and anti-Müllerian hormone levels were higher (P < 0.05) on PND26 than in non-DHT daughters (controls). DHT daughters showed an extended time in metestrus/diestrus and a shorter time in the proestrus/estrus phase compared with non-DHT daughters (P < 0.05). To examine ovarian response to gonadotropins, superovulation was induced and in vitro fertilization (IVF) was performed. Fewer numbers of oocytes were retrieved from the DHT daughters compared with non-DHT daughters (P < 0.05). At IVF, there was no difference in rates of fertilization or cleavage of oocytes from either group. There were fewer (P < 0.01) primordial follicles (6.5 ± 0.8 vs 14.5 ± 2.1 per ovary) in the ovaries of DHT daughters compared with non-DHT daughters. Daughters from hyperandrogenemic females exhibited elevated prepubertal FSH levels, diminished ovarian response to superovulation, impaired estrous cyclicity, delayed onset of puberty, and reduced ovarian reserve, suggesting that fetal androgen exposure had lasting effects on female reproductive function.

Extragonadal Actions of FSH: A Critical Need for Novel Genetic Models.

Follicle-stimulating hormone (FSH) is critical for ovarian folliculogenesis and essential for female fertility. FSH binds to FSH receptors (FSHRs) and regulates estrogen production in ovarian granulosa cells to orchestrate female reproductive physiology. Ovarian senescence that occurs as a function of aging results in loss of estrogen production, and this is believed to be the major reason for bone loss in postmenopausal women. Although conflicting, studies in rodents and humans during the last decade have provided genetic, pharmacological, and physiological evidence that elevated FSH levels that occur in the face of normal or declining estrogen levels directly regulate bone mass and adiposity. Recently, an efficacious blocking polyclonal FSHβ antibody was developed that inhibited ovariectomy-induced bone loss and triggered white-to-brown fat conversion accompanied by mitochondrial biogenesis in mice. Moreover, additional nongonadal targets of FSH action have been identified, and these include the female reproductive tract (endometrium and myometrium), the placenta, hepatocytes, and blood vessels. In this mini-review, I summarize these studies in mice and humans and discuss critical gaps in our knowledge, yet unanswered questions, and the rationale for developing novel genetic models to unambiguously address the extragonadal actions of FSH.

Endocrine predictors of testicular biopsy efficacy in patients with azoospermia

OBJECTIVE. The study identified predictors of endocrine detection of sperm in case of open testicular biopsy in patients with non-obstructive azoospermia. MATERIAL AND METHODS. The research was based on the results of examination and testicular biopsy of 76 patients with secretory azoospermia aged from 20 to 55 years old. The instrumental, laboratory, physical methods of research were carried out for all the patients before performing of the open biopsy for testicular sperm extraction. Hormone levels were determined in blood plasma such as luteinizing hormone, follicle stimulating hormone, prolactin, total and free testosterone, estradiol and sex steroid binding globulin. Patients were divided into two groups. The first group consisted of patients (n =43) whom sperms were found in testicular biopsies. The second group included patients (n = 33) whom sperms weren’t detected. RESULTS. Сonсentration of follicle stimulating hormone in blood plasma was the most significant hormone predictor. It was found that follicle stimulating hormone level between 12 and 16 IU/L indicated to the low probability of sperm presence in testicular biopsies and in case it was less than 17 IU/L the probability was extremely low. There was also established that elevated follicle stimulating hormone levels in patients older than 26 years pointed to the low probability of finding sperm using open testicular sperm extraction. CONCLUSIONS. Increase of luteinizing hormone, follicle stimulating hormone or their correlation in blood plasma indicates to a low probability of finding sperm by open testicular sperm extraction. The concentrations of testosterone, sex steroid binding globulin, prolactin and estradiol in the blood plasma weren’t reliable predictors of finding sperm in testicular biopsies.

The Non‐Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Ameliorates Spermatogenesis Function in a Mouse Model of Chronic Social Defeat Stress

To determine the effects of SSR149415 on testis and spermatogenesis in male mice subjected to chronic social defeat stress, C57BL/6 male mice were divided into two groups: Control and Stress. Then Stress group was subdivided into four subgroups administered water, SSR149415 (1 mg/kg/day), SSR149415 (10 mg/kg/day), SSR149415 (30 mg/kg/day), respectively. The behavioral alterations revealed by social interaction test and open field test were measured. The physical indices, including body weight and gonad weight (testis and epididymis) as well as testis/body weight and cauda epididymis/body weight were detected. Serum hormones, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Sperm count and abnormality as well as testicular histology structure were assessed. The germ cells apoptosis were also evaluated. Chronic social defeat stress-induced behavioral abnormality, as well as gonad atrophy (testis and epididymis) was significantly alleviated in stressed male mice exposed to SSR149415. Regressed serum testosterone levels and elevated serum FSH and LH levels exhibited by stressed male mice were observably reversed following SSR149415 administration. Chronic social defeat stress-induced damage in testicular histology structure and semen quality were also improved after SSR149415 administration. In addition, SSR149415 significantly reversed chronic social defeat stress-induced germ cells apoptosis. Overall, we provide clear evidence indicating the amelioration of chronic social defeat stress-induced behavioral abnormality and testicular dysfunction via SSR149415, promoting the development of drug-directed therapy against this disease. J. Cell. Biochem. 118: 3891-3898, 2017. © 2017 Wiley Periodicals, Inc.

Testicular dysfunction in men affected by lepromatous leprosy

Objective: To assess the levels of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in adult males affected by lepromatous leprosy. Methodology: This cross-sectional study included 40 men (age 41.78 ± 13.35 years; mean ± SD) affected by lepromatous leprosy from leprosy clinics in Dhaka and Nilphamari, Bangladesh, who were either receiving multi-drug therapy (MDT) for leprosy (n = 23) or were released from treatment (RFT; n = 17). Clinical data were recorded while serum testosterone, LH and FSH were assayed by enzyme immunoassay (EIA). Results: Serum testosterone was low in 12 (30%) participants, while 16 (40%) had a normal testosterone level but elevated LH and FSH. Testicular volume was lowest in those with a low testosterone level, followed by those with a normal testosterone but elevated LH and FSH levels, and highest in those who had all these hormones within the normal range (11.42 ± 1.33 ml vs. 16.97 ± 1.25 ml vs. 22.50 ± 1.01 ml respectively; mean ± SEM; P &lt; 0.001). The frequency of erythema nodosum leprosum (ENL) was observed to follow a similar pattern (low testosterone vs. normal testosterone but elevated LH, FSH vs. all normal: 83.3% vs. 68.8% vs. 33.3%, P = 0.033). There was a significant negative correlation between the testosterone level and the bacillary index (r = −442, P = 0.010) and the presence of ENL (r = 20.331, P = 0.037), and a positive correlation with testicular volume (r = 464, P = 0.003). LH and FSH also had significant negative correlation with testicular volume (r = −0.554, P &lt; 0.001 and r = −0.601, P &lt; 0.001 respectively). In conclusion, nearly one third men affected by lepromatous leprosy people had low testosterone. The testosterone level correlated positively with testicular volume and negatively with bacillary load and ENL.

Efficacy of nasal continuous positive airway pressure on patients with OSA with erectile dysfunction and low sex hormone levels

PurposeThis study aimed to test the hypothesis that erectile dysfunction (ED) is common in men with obstructive sleep apnea (OSA). We also assessed the efficacy of continuous positive airway pressure (CPAP) treatment for ED and sex hormone levels in patients with severe OSA and ED. MethodsA total of 153 OSA patients and 60 healthy controls were enrolled in this study. The International Index of Erectile Dysfunction-5 (IIEF-5) score was obtained, and blood samples were collected for analysis of sex hormones after polysomnography. The IIEF-5 score, sex hormone levels, and polysomnographic parameters were re-evaluated in 32 patients with severe OSA and ED after 1 month of CPAP treatment. ResultsThe present study showed that the prevalence of ED was 47.1% in all cases and only 13.3% in controls, and a lower sex hormone levels was presented in OSA patients. OSA patients with ED had greater severity of disease, and lower serum levels of follicle stimulating hormone (FSH) and testosterone than OSA patients without ED (p < 0.05). After CPAP therapy, there was a significant increase in the IIEF-5 score, and serum levels of FSH, luteinizing hormone, and testosterone, were elevated compared with baseline levels (p < 0.05). Multivariate regression analysis indicated the serum level of testosterone had impact on the ED. ConclusionsOSA patients had lower sex hormone levels and a higher occurrence of ED than controls, and serum level of testosterone had effect on ED. CPAP treatment ameliorated the symptoms of ED and elevated serum levels of FSH, luteinizing hormone, and testosterone.

Synthetic hydrogel supports the function and regeneration of artificial ovarian tissue in mice.

Many prepubertal girls and young women suffer from premature ovarian insufficiency induced by chemotherapy given for treatment of cancer and autoimmune diseases. Autotransplantation of cryopreserved ovarian tissue could restore the lost ovarian endocrine function and fertility. Unfortunately, tissue ischemia, inconsistent graft quality and the risk of reintroducing malignant cells may stand in the way of the clinical translation of this approach. To address these risks and limitations, we engineered an artificial ovarian tissue from immature follicles using a synthetic hydrogel, poly(ethylene glycol) vinyl sulfone (PEG-VS), as a supportive matrix. Enzymatically isolated follicles from 6–7-day-old mice ovaries were encapsulated in 7% PEG-VS hydrogels modified with 0.5 mmol/l RGD and crosslinked with a trifunctional matrix metalloproteinase-sensitive peptide. PEG hydrogels with the encapsulated follicles were orthotopically implanted into ovariectomised mice to investigate whether PEG hydrogel supports folliculogenesis and steroidogenesis in vivo. After 30 days, grafts revealed multiple fully developed antral follicles and corpora lutea, which corresponded with regular ovulation cycles and follicle-stimulating hormone (FSH) levels. The elevated levels of FSH, caused by bilateral ovariectomy, were reversed by the implanted follicles and maintained at physiological levels for 60 days. Importantly, primordial and primary follicles still represented 60% of the follicular pool, demonstrating selective recruitment of primordial follicles into the growing pool. Functioning blood vessels in the grafts 30 and 60 days after implantation proved the capability of PEG hydrogels to undergo graft remodelling and revascularisation. Our results demonstrate that PEG hydrogels with encapsulated immature ovarian follicles successfully functioned as an artificial ovarian tissue for 60 days in vivo.

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism.

Objective:Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD.Methods:The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured.Results:There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score.Conclusion:BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD.

Bone turnover alterations across the menopausal transition in south-eastern Chinese women

Objectives: To explore the serum levels of bone resorption marker C-terminal telopeptide of type I collagen (CTX) and bone formation marker N-amino terminal propeptide of type I collagen (PINP) in Chinese women across the menopausal transition and the correlation between follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol with the bone turnover markers.Methods: A cross-sectional study was conducted on 464 healthy Chinese women, separated into pre-, peri- and postmenopausal groups based on their menstruation changes. The serum levels of CTX, PINP, FSH, LH, and estradiol were measured.Results: The serum levels of CTX and PINP were significantly higher in women in the peri- and postmenopausal groups. The serum levels of FSH were significantly correlated with the serum levels of PINP in premenopausal women. Both serum FSH and LH were positively correlated with serum CTX in perimenopausal women and postmenopausal women. Estradiol was inversely correlated with CTX in the perimenopausal group. Multiple linear regression models show the serum FSH levels were independently related to the bone turnover markers CTX and PINP.Conclusions: The elevated serum levels of FSH were independent risk factors for bone loss in peri- and postmenopausal women, and measurement of the serum FSH levels in mid-age women with irregular menses could be used in early diagnosis of postmenopausal osteoporosis.

Protocol for systematic review and meta-analysis: hop (Humulus lupulus L.) for menopausal vasomotor symptoms

IntroductionMenopause is a critical stage in every woman's life. It can cause a distressing time for women by creating various vasomotor symptoms (VMS). Phytoestrogens can potentially exert various favourable effects...

First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery

Ovarian tissue cryopreservation is an experimental fertility preservation method and the transplantation techniques are still evolving. We attempted to improve the technique with the utility of a human decellularized extracellular tissue matrix (ECTM) scaffold, robot-assisted minimally invasive surgery, and perioperative pharmacological support. We prospectively studied 2 subjects with hemophagocytic lymphohistiocytosis (patient A) and non-Hodgkin lymphoma (patient B) who underwent ovarian tissue cryopreservation at the age of 23 years, before receiving preconditioning chemotherapy for hematopoietic stem cell transplantation. Both experienced ovarian failure postchemotherapy and we transplanted ovarian cortical tissues to the contralateral menopausal ovary 7 and 12 years later, using a human ECTM scaffold and robotic assistance. The ECTM scaffold tissue compatibility was shown in preclinical studies. Patients also received estrogen supplementation and baby aspirin preoperatively to aid in the revascularization process. Ovarian follicle development was observed approximately 10 (patient A) and 8 (patient B) weeks after ovarian tissue transplantation. Following 8 and 7 cycles of invitro fertilization, 9 and 10 day-3 embryos were cryopreserved (patients A and B, respectively). While the baseline follicle-stimulating hormone (range 3.6-15.4 mIU/mL) levels near normalized by 7 months and remained steady postovarian transplantation in patient A, patient B showed improved but elevated follicle-stimulating hormone levels throughout (range 21-31 mIU/mL). Highest follicle yield was achieved 14 (8 follicles; patient A) and 11 (6 follicles; patient B) months postintervention. Patient A experienced a chemical pregnancy after the third frozen embryo transfer attempt. She then conceived following her first fresh invitro fertilization embryo transfer and the pregnancy is currently ongoing. Patient B conceived after the first frozen embryo transfer attempt and delivered a healthy girl at term. We report the first pregnancies after the minimally invasive transplantation of previously cryopreserved ovarian tissue with an ECTM scaffold. This approach seems to be associated with steady ovarian function after a follow-up of up to 2 years.

A study on serum FSH, LH and Prolactin Levels Among infertile women

Background: Study of hormonal imbalance and its implications in female infertility are an interesting area that requires to be explored in recent time. Hormonal imbalance can associated with irregular menstrual cycle, Amenorrhea, obesity and infertility in women. Other medical conditions such as polycystic ovarian syndrome, Endometriosis, stress, sexually transmitted diseases and chromosomal anomalies may be responsible for infertility in females. Objective: The aim of the present study was to evaluate the serum levels of Follicle Stimulating hormone (FSH), Luteinizing hormone (LH) and Prolactin hormone in infertile women that were referred from different infertility clinics and centres. Materials and Methods: This study comprises total 176 female subjects with age ranging from 20 to 40 years and divided in two groups. The total number of 88 infertile women along with 88 fertile women as controls was included for the present study. Serum FSH, LH and Prolactin levels were estimated by enzyme-linked immunosorbent assay (ELISA) methods. Results: The results showed maximum infertile women were found between the age group of 30-40 years. The Serum FSH, LH and Prolactin levels among infertile women was 8.77±4.65, 7.64±5.16 and 18.59±7.50 respectively. Whereas, levels of FSH, LH and Prolactin in fertile women showed that 6.71±4.12, 5.66±3.17 and 13.44±5.82 respectively. Conclusion: In this study, we found that the hormone levels have statistically significant with female infertility. The elevated levels of FSH, LH and Prolactin may be one of the important causes for infertility in women.

A Case of Ankylosing Spondylitis and Ichthyosis Vulgaris in a Turner Syndrome Patient with a Rare Karyotype

ABSTRACT Objective: Turner syndrome (TS) is a chromosomal disorder in which patients have either a missing X chromosome (45,X), a structural aberration of sex chromosome, or mosaicism including mos 45,X/46,XY. We present a case of TS with unusual ankylosing spondylitis (AS) and ichthyosis vulgaris (IV) carrying a rare karyotype of 45,X[100]/46,X,idic(Yp)[12](pter-q11::q11-pter). Methods: A review of the literature was conducted to identify previous case reports pertaining to TS accompanied with AS and compare them with the current case. Results: The patient presented with positive human leukocyte antigen (HLA) B27, lowered estrogen, and elevated follicle-stimulating hormone and luteinizing hormone levels. Ultrasound examination showed no uterus or ovaries. The patient carried a mosaic karyotype of 45,X[100]/46,X,idic(Yp)[25].ish(DXYS129+,DXYS153+ +,SRY++,DYZ3++,Yq12-) for metaphase peripheral blood lymphocytes and 45,X[100].ish(DYZ3-) for interphase buccal cells. Molecular genetic analysis revealed that t...

Fibrin-mediated delivery of an ovarian follicle pool in a mouse model of infertility.

The cryopreservation and autotransplantation of ovarian tissue is emerging as a powerful approach for preserving fertility. However, for cancer patients, it may not be possible to transplant ovarian tissue due to the risk of re-seeding disease. We investigated strategies for transplantation of individually isolated follicles to minimize the risk of re-introducing cancer cells present within the vasculature of ovarian stroma. Procedures for large-scale isolation of early-stage follicles and their encapsulation into fibrin hydrogels were developed. For in vivo validation studies, mice were ovariectomized and transplanted with encapsulated follicles into the ovarian bursa. A substantial increase in the number of secondary follicles was observed in the graft at 9 days after transplantation, and antral follicles by day 21, demonstrating primordial follicle recruitment into the growing pool. Initially, elevated follicle-stimulating hormone levels declined substantially by day 21, indicating feedback from the graft; presence of corpora lutea showed the graft's capability of restoring hormone cyclicity. Taken together, the transplanted follicles were able to engraft, mature, and restore ovarian function in an infertile mouse. This biomaterial may, thus, provide a platform for follicle transplantation with a low risk of cancer contamination and for developing strategies that preserve fertility for women facing a cancer diagnosis.

Evidence to Incorporate Inclusive Reproductive Health Measures in Guidelines for Childhood and Adolescent Cancer Survivors

ObjectiveFemale childhood cancer survivors are at an increased risk of reproductive health impairment. We compared reproductive health outcomes with the recommended standard in a cohort of childhood cancer survivors. Study Design and ParticipantsA retrospective chart review of 222 female childhood cancer survivors aged 21 years or younger that presented to a tertiary referral center between 1997-2008 was initiated. The main outcome measures were the compliance with the American Society of Clinical Oncology guidelines for childhood cancer survivor management of reproductive health. In particular, we evaluated menstrual cycle regularity, fertility preservation counseling, and endocrine profile, as defined by follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) levels as surrogate markers for ovarian reserve. Secondary outcomes were to study the contribution of survivor clinics in enforcing these guidelines. ResultsOf 136 patients older than 13 years at their last visit, 58 patients (43%) had FSH data available and none had AMH data. Patients were stratified into 3 groups according to FSH levels. Forty of 58 patients (69%) have normal ovarian reserve (FSH level < 10), 10 of 58 patients (17%) have decreased ovarian reserve (FSH levels 10-40), and 8 of 58 patients (14%) have premature menopause, defined as FSH > 40. Most patients with amenorrhea have elevated FSH levels indicating primary ovarian insufficiency, while 3 patients (2.2%) have low FSH levels consistent with hypothalamic amenorrhea. None of the patients were counseled on fertility preservation. ConclusionsReproductive health follow-up in children with cancer, including FSH and AMH measurement when indicated, should be established and strictly adhered.