Resumption Of Ovarian Function Research Articles

Supplementation of rumen-protected lysine during the close-up period improves vaginal discharge clearance in Holstein dairy cows.

We aimed to evaluate the effects of rumen-protected lysine (RPL) supplementation during the close-up period on uterine involution and the resumption of ovarian function in dairy cows. Fifty-two multiparous Holstein cows were categorized based on parity and expected calving date and randomly assigned to the RPL or control (CON) groups. The RPL group received 80 g of RPL daily from day 21 before the expected calving date until parturition. Blood samples were obtained twice weekly from pre-supplementation to 6 weeks postpartum. The onset of luteal activity postpartum was determined via ultrasonography twice weekly for up to 6 weeks postpartum. Uterine involution was tracked at 3 and 5 weeks postpartum through the vaginal discharge score, percentage of polymorphonuclear cells (PMN) in endometrial cytology samples, presence of intrauterine fluid, and gravid horn diameter via ultrasonography. Before supplementation, the RPL group showed amino acid imbalance, which was improved by RPL supplementation. There were no significant differences in the onset of luteal activity, percentage of PMN, intrauterine fluid, or the diameter of the uterine horn between the two groups. The vaginal discharge score in the RPL group decreased from 3 to 5 weeks postpartum, whereas that in the CON groups did not decrease. The number of cows with clinical endometritis was lower in the RPL group. Overall, RPL supplementation during the close-up period enhanced vaginal discharge clearance, potentially averting clinical endometritis, but did not affect the first ovulation in dairy cows.

Possible involvement of somatotrophic hormones in the postpartum regulation of ovarian activity in mares

In horses, resumption of ovarian function after parturition occurs early and the majority of mares ovulate within two weeks after parturition. Previous research suggests that early postpartum increases in the peripheral concentration of prolactin and somatotrophic hormones are the major stimulus for resumption of ovarian activity and ovulation. In the present study, we investigated if placental tissue may be a source of somatotrophic hormones and thus influence ovarian activity. Ovarian follicular development and concentrations of prolactin, insulin like growth factor-1 (IGF1) and LH were determined in 14 healthy Haflinger mares (9.2±3.8 years). From D15 before until D15 after parturition (pp), transrectal ultrasonography of ovarian activity was performed and blood samples were collected for determination of hormone concentrations (prolactin, IGF1 by ELISA; LH by RIA). All foals were healthy, mature and stayed with their dams. Samples from the allantochorion and amnion were obtained immediately after delivery. The relative abundance of mRNA for IGF1 and the prolactin receptor (PRLR) was analyzed by qPCR. Formalin fixed samples were analyzed for protein expression of IGF1 and PRLR by immunohistochemistry. Statistical analysis (IBM SPSS 27.0) was done by analysis of variance (for repeated measures) comparing data from mares that ovulated(group ov; n=5) and did not ovulate until D15 pp (group non-ov, n=9). Values are mean ± SD. Mares from group ov foaled later in the year than non-ov mares (day of year 84±29 vs. 50±20, p<0.05), but no differences in gestation length, placental weight or size were detected. Already on D15 before parturition, ovarian follicles <2 cm diameter were present in all mares, but growth to preovulatory size occurred only pp with a higher growth rate in ov mares (day x group p<0.05). Prolactin and IGF1 concentrations increased from D5 before parturition, peaked at D1 pp (ov vs. non-ov: prolactin 13.0±6.3 vs. 7.9±4.4 ng/ml, p<0.05; IGF1 409±71 vs. 350±65 ng/ml, p<0.05) and declined thereafter. The LH concentration increased from D1 pp in group ov (D12 pp: 23.82±15.96 ng/ml) but not in non-ov (D12 pp: 10.82±5.26 ng/ml; day x group p<0.001). There was a high abundance of mRNA and protein for IGF1 and PRLR in placental tissue irrespective of group. In conclusion, ovarian follicles are detectable before foaling, but develop to preovulatory size only pp when prolactin and LH concentrations increase. In agreement with the situation in cattle, IGF1 stimulates ovarian activity in lactating mares. Placental tissue produces IGF1 that may be under the influence of prolactin as suggested by the presence of PRLR in both amnion and allantochorion.

Gonadotropin-releasing hormone agonists for ovarian protection during breast cancer chemotherapy: a systematic review and meta-analysis.

ImportanceThe increasing trend of delaying childbirth means that more women are being diagnosed with breast cancer before having given birth to their desired number of children. Although chemotherapy can significantly improve the prognosis of this population, it also causes ovarian damage, including premature ovarian insufficiency and infertility. Gonadotropin-releasing hormone agonists (GnRHa) have shown promising fertility protective activity in premenopausal women, but their clinical usage remains controversial.ObjectiveHere, we conducted a meta-analysis to assess the efficacy of GnRHa when administered concurrently with chemotherapy that included cyclophosphamide in the prevention of chemotherapy-induced ovarian damage in premenopausal women.Evidence ReviewAn extensive literature search was performed using the PubMed, Embase, and Cochrane databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were determined.FindingsEleven randomized controlled trials with a total of 1,219 participants were included in the analyses. A significantly higher number of women treated with GnRHa experienced the resumption of ovarian function after chemotherapy than those who did not receive this treatment (OR, 3.04; 95% CI, 1.87‐4.94; P < 0.001). Regarding spontaneous pregnancy, a statistically significant difference was observed only in hormone receptor-negative participants (OR, 2.06; 95% CI, 1.03‐4.11; P = 0.04).Conclusions and RelevanceWhen treating premenopausal women with breast cancer, the administration of GnRHa concurrently with chemotherapy appeared to improve the resumption rate of ovarian function; however, the spontaneous pregnancy rate only improved in hormone receptor-negative patients. Thus, the use of GnRHa during chemotherapy may represent a feasible strategy for preserving ovarian function in women with breast cancer.

Biomechanical characteristics of the ovarian cortex in POI patients and functional outcomes after drug-free IVA.

There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. The rigidity of the cortical ECM limits expansion of the follicle and consequently oocyte maturation, maintaining the follicle in its quiescent state. Quiescent primordial, primary, and secondary follicles still exist in primary ovarian insufficiency (POI) patients, and techniques as in vitro activation (IVA) and drug-free IVA have recently been developed aiming to activate these follicles based on the Hippo signaling disruption that is essential in mechanotransduction. In this context, we analyze the effect of drug-free IVA in POI patients, comparing the relationship between possible resumption ovarian function and biomechanical properties of ovarian tissue. Nineteen POI patients according to ESHRE criteria who underwent drug-free IVA by laparoscopy between January 2018 and December 2019 and were followed up for a year after the intervention. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure tissue stiffness (Young's elastic modulus, E) at the micrometer scale. Functional outcomes after drug-free were analyzed. Resumption of ovarian function was observed in 10 patients (52.6%) and two of them became pregnant with live births. There were no differences in clinical characteristics (age and duration of amenorrhea) and basal hormone parameters (FSH and AMH) depending on whether or not there was activation after surgery. However, ovarian cortex stiffness was significantly greater in patients with ovarian activity after drug-free IVA: median E = 5519Pa (2260-11,296) vs 1501 (999-3474); p-value < 0.001. Biomechanical properties of ovarian cortex in POI patients have a great variability, and higher ovarian tissue stiffness entails a more favorable status when drug-free IVA is applied in their treatment. This status is probably related to an ovary with more residual follicles, which would explain a greater possibility of ovarian follicular reactivations after treatment.

P-605 Biomechanical characteristics of the ovarian cortex in POI patients and functional outcomes after drug-free IVA

Abstract Study question Is there a relationship between the biomechanical characteristics of ovarian cortex of POI patients and the resumption ovarian function after Drug-Free IVA? Summary answer Physical properties of ovarian cortex in POI are different. A significant ovarian stiffness increase was observed when resumption of ovarian function occurred after Drug-Free IVA. What is known already There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. Primordial follicles are localized at the collagen-rich ovarian cortex, which offers a rigid physical environment that supports follicular architecture and increases survival. Therefore, premature loss of ovarian function would be associated with a physically less rigid ovarian cortex. Study design, size, duration Prospective observational cohort study at a tertiary-care university hospital including POI patients according ESHRE criteria who underwent Drug-Free IVA by laparoscopy between January 2018 and December 2019 and were follow-up for a year after intervention. Participants/materials, setting, methods Nineteen patients were included. Resumption of ovarian function was defined as resumption of menstrual cycles (at least three consecutive episodes of menstrual bleeding) and/or the presence of follicles &amp;gt; 10 mm on ultrasound. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure mechanical properties at the nanometer scale (Young’s elastic modulus, E). Main results and the role of chance Median data at intervention were: age = 35 years (28–39); length of amenorrhea = 2 years (1–10); FSH level = 104.4 mIU/ml (38.9–176); and AMH = 0.02 ng/ml (0.01–0.1). Resumption of ovarian function was observed in 10 patients (52.6 %), achieving 2 pregnancies (one spontaneous and one after an IVF cycle). Median stiffness (E) measured by AFM was 2583 Pa (999–11296). There were no differences in clinical and hormonal parameters as a function of resumption of ovarian activity. Remarkably, ovarian cortex stiffness was significantly increased in patients with ovarian activity after Dug-Free VIA: 5519 (2260–11296] vs 1501 [999–3474], p value &amp;lt;0.001. Limitations, reasons for caution The main limitations of the study are the unavailability of ovarian tissue samples from a control group of patients without POI and the inability to perform histological studies on the same samples in which the biomechanical study was carried out. Wider implications of the findings These findings show the high variability of ovarian cortex stiffness in POI and that the increase of this stiffness entails a more favorable status after Drug-Free IVA. This may be related to an ovary with more residual follicles, which would explain a greater chances of ovarian follicular reactivations after treatment. Trial registration number not applicable

Resumption of ovarian activity following removal of a 4.7 mg deslorelin implant in queens.

Deslorelin implants are widely used in felines. Due to their prolonged duration cat breeders frequently request early implant removal. The interval between deslorelin implant removal and resumption of ovarian function in queens is unknown. The aim of this study was to evaluate the interval between the removal of a deslorelin implant and the resumption of ovarian activity in adult queens. Twenty-three queens were treated with a 4.7mg deslorelin implant placed in the periumbilical area. In the 16 queens completing the study implants were surgically removed at 3, 6 or 9months (n=6, 4 and 6 queens, respectively). Queens received a GnRH stimulation test as part of their pre-treatment general and reproductive health check. Following implantation treatment, all queens in inter-oestrus-anoestrus at the time of treatment came in oestrus within 2-5 days. Starting 7-14days following implant removal queens were checked every 1-2weeks with reproductive ultrasonography, a vaginal smear and blood collection. The interval to resumption of ovarian function ranged from 3 to 7weeks irrespective of treatment length and age of the queen but was longer when the implant was removed at decreasing photoperiod (p<.05). In conclusion, at least 3weeks post-removal are needed during increasing photoperiod to achieve follicular development and oestrogen production sufficient to support oestrous behaviour in queens following removal of a 4.7mg deslorelin implant, while this time may increase up to 7weeks during decreasing photoperiod. Further studies are needed to assess the interval between removal of a deslorelin implant and occurrence of ovulation as well as fertility at the first oestrus after a deslorelin treatment.

Associations between metabolic profiles, post-partum delayed resumption of ovarian function and reproductive performance in Egyptian buffalo: Roles of IGF-1 and antioxidants

This study was conducted on 47 pluriparous pregnant Egyptian buffalo. Body condition score (BCS) was classified and blood samples were collected pre-partum and post-partum for estimation of IGF-1, hormonal, metabolic and antioxidants values. There was palpation per rectum and ultrasonography in addition to quantitation of progesterone (P4) and estradiol-17β (E-17β) for monitoring post-partum ovarian resumption. Reproductive indices were calculated 60, 90, 120 and 150 days post-partum. Based on the concentrations of P4 and E-17β, buffalo were divided into ovulatory and non-ovulatory groups. The P4 and E-17β were greater (P < 0.001) in ovulatory compared to non-ovulatory buffalo. The BCS and IGF-1 post-partum were greater (P = 0.024; 0.001, respectively) in ovulatory than non-ovulatory buffalo. Glucose and albumin were greater during pre- (P < 0.001; 0.013) and post-partum (P = 0.005; 0.003) periods in ovulatory than non-ovulatory buffalo. Post-partum, NEFA and BHBA concentrations were greater (P < 0.001) in non-ovulatory than ovulatory buffalo. The BUN concentrations were greater (P = 0.002) in non-ovulatory buffalo during pre- and post-partum periods. There were differences in GSH and SOD concentrations between groups (P < 0.001; 0.002, respectively). The BCS, albumin, IGF-1, GSH and SOD concentrations post-partum were negatively correlated with the delay of post-partum ovulation. The post-partum NEFA and BHBA concentrations, however, were positively correlated with delayed post-partum ovulation. Ovulatory buffalo had fewer (P < 0.01) days non-pregnant and for calving intervals as well as greater pregnancy rates than non-ovulatory buffalo. In conclusion, buffalo with delayed post-partum ovarian resumption were prone to have negative energy balance.

INFLUENCE OF VITAMIN E AND SELENIUM SUPPLEMENTATION ON THE PERFORMANCE, REPRODUCTIVE INDICES AND METABOLIC STATUS OF OSSIMI EWES

The objective of this study was to investigate the effects of pre and post-lambing intramuscular (i.m.) injections of vitamin E (VE) and selenium (Se) on the performance, reproductive indices and metabolic status of Ossimi ewes. A total of 20 pregnant ewes were divided randomly into two equal groups of ten animals. The control group (CG) was administered 3 ml of normal saline. The treated group (TG) was administered a combination of 5 mg of sodium selenite and 450 mg of VE twice weekly for 2 weeks pre and post lambing. The performance, reproductive indices, colostrum and milk mineral profiles, blood metabolites and antioxidant enzyme biomarkers were investigated in this experiment. VE and Se supplementation had a significant effect on ewe, lamb performance, colostrum and milk mineral profiles. The treated ewes lost less weight (0.7 kg) compared with the ewes in the control group (3.68 kg) on 30th day postpartum (P&lt;0.001). Lambs born to treated ewes were heavier than those born to control ewes (4.47 kg vs 3.99 kg, respectively), gained more daily weight quickly (268.66 vs. 226.00 g, respectively, P&lt;0.001) and weighed more on 30th day post-lambing (12.53 vs. 10.77 kg, respectively, P&lt;0.001). Treated ewes had higher concentrations of blood glucose, total protein, total cholesterol, antioxidant enzyme biomarkers, and lower concentrations of serum non-esterified fatty acids (NEFA). VE and Se supplementation had a significant effect (P&lt;0.05) on postpartum reproductive performance of ewes in terms of fast uterine involution, earlier resumption of ovarian function and ovulation with large size ovulatory follicles, and greater numbers of small, medium, and large-sized follicles. In conclusion, VE and Se supplementation during late gestation and early lactation could be considered an effective strategy for minimizing the weight loss of ewes, enhancing lamb performance, the antioxidant and metabolic status, which improves the reproductive performance of Ossimi ewes.Key words: vitamin E; selenium; lamb performance; reproductive performance; antioxidant status; Ossimi ewes

Resumption of Ovarian Function After Ovarian Biopsy/Scratch in Patients With Premature Ovarian Insufficiency.

To evaluate the effect of ovarian biopsy and scratch on the resumption of ovarian function in women with premature ovarian insufficiency (POI), the follicle development and pregnancy outcome were retrospectively analyzed in women with POI after ovarian biopsy/scratch. Eighty patients with POI with secondary amenorrhea were accepted the laparoscopic surgery, and then hormone replacement treatment for 6 months was applied and in vitro fertilization and embryo transfer was suggested. No significant difference in clinical characteristics was observed before and after ovarian biopsy/scratch ( P > .05). After the ovarian surgery, 11 (13.75%) patients presented with ovarian function resumption spontaneously or with human menopausal gonadotropin stimulation. Three metaphases II oocytes were retrieved in 10 patients. Two embryos were formed and freshly transferred followed by a healthy singleton delivery in 1 (1.25%) patient. Patients with follicle development had higher baseline estradiol compared to those without (78.20 [18.53-161.08] pg/mL vs 15.70 [8.40-43.80] pg/mL, P < .01). The technique of ovarian biopsy/scratch could promote follicle development in vivo, suggesting it could bring promising benefits for some women with POI. However, future improvement in efficiency and practice criteria is warranted.

Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report.

Stem cell transplantation has been considered a promising therapeutic approach for premature ovarian failure (POF). However, to date, no quantitative data analysis of stem cell therapy for POF has been performed. Therefore, the present study performed a meta-analysis to assess the efficacy of stem cell transplantation in improving ovarian function in animal models of POF. In addition, a case report of a patient with POF subjected to stem cell treatment was included to demonstrate that stem cell therapy also contributes to the recovery of ovarian function in patients. Published studies were identified by a systematic review of the PubMed, Embase, and Cochrane's library databases, and references cited in associated reviews were also considered. Data regarding follicle-stimulating hormone (FSH), estradiol (E2), ovarian weight, follicle count, the number of pregnancies and other parameters, including delivery route and cell type, were extracted. Pooled analysis, sensitivity analyses, subgroup analyses and meta-regression were performed. In the case of POF, transvaginal ultrasound (TVS), abdominal ultrasound (TAS) and color Doppler flow imaging (CDFI) were performed to observe the endometrial morphology and blood flow signals in the patient. Overall, pooled results from 16 pre-clinical studies demonstrated that stem cell-based therapy significantly improved FSH levels [standardized mean difference (SMD)=−1.330; 95% confidence interval (CI), -(2.095–0.565); P=0.001], E2 levels (SMD=2.334; 95% CI, 1.350–3.319; P<0.001), ovarian weight (SMD=1.310; 95% CI, 0.157–2.463; P=0.026), follicle count (SMD=1.871; 95% CI, 1.226–2.516; P<0.001), and the number of pregnancies (risk ratio=1.715, 95% CI, 1.213–2.424; P=0.002). The results of TVS and TAS demonstrated improved ovarian size and endometrial thickness in the patient with POF after MSC treatment. Of note, a rich blood flow signal in the endometrium was observed on CDFI. It appeared that stem cell-based therapy may be an effective method for the resumption of ovarian function in a patient and in animal models of POF; however, large-scale and high-quality future studies are required to confirm the present findings due to heterogeneity.

Resumption of ovarian function, the metabolic profile and body condition in Brahman cows (Bos indicus) is not affected by the combination of calf separation and progestogen treatment

To evaluate the effect of different calf separation procedures after a progestogen treatment on the resumption of ovarian function, body condition and metabolic profile, 59 multiparous Brahman cows grazing on a mixed grass pasture were studied. No supplementation was given at any time. Body condition score (BCS), fat thickness (FAT) and blood metabolites were measured fortnightly from the beginning of the last trimester of gestation until 96days postpartum. At 30days postpartum all animals received a progesterone (P4)-releasing device (CIDR) which was withdrawn 9days later when prostaglandin F2α was applied. At this time, treatments TW (n=28), where calves were separated from their dams for 48h; RS (n=21), calves were allowed to suckle once a day for 1h; and continuous suckling (CS; n=10). Ovarian function was assessed by blood concentrations of progesterone on days −14, −9, 10, 13, 30 and 33 after CIDR removal. At the end of the experimental period, an average of 20% of the cows had not initiated estrous cycles. There were no changes of FAT or BCS during the last trimester of pregnancy in all cows (P>0.05). During the postpartum period cows of all groups lost (P<0.05) BCS and FAT with a nadir at 60–80days postpartum, regardless of treatment. At 10days after CIDR withdrawal the percentage of cows having ovulations was 75, 61 and 80 (P>0.05) for TW, RS and CS groups. Blood metabolites follow a similar pattern in the three groups. With the conditions of the present study, the method of calf separation after a progestogen treatment, does not affect the resumption of ovarian function or metabolic profile.

The ‘normal’ range of FMR1 triple CGG repeats may be associated with primary ovarian insufficiency in China

The aim of this study was to investigate the relationship between normal Fragile X mental retardation gene 1 (FMR1) CGG repeat numbers and primary ovarian insufficiency (POI) occurrence or subsequent resumption of ovarian function. A total of 122 women with POI and 105 controls were followed up and analysed in our centre. The prevalence of premutation and intermediate range of FMR1 CGG repeats in Han Chinese women with POI was only 0.81% (1/122) and 1.64% (2/122), respectively. The risk of POI occurrence for less than 26 CGG repeats and 29 or more CGG repeats in allele1 (smaller allele) was significantly higher than that for 26–28 CGG repeats (odds ratio 13.50, 95% confidence interval: 3.21 to 56.77 and 6.32, 95% confidence interval: 2.49 to 16.09 respectively; both P < 0.001). No significant difference was found in the CGG repeat distribution (<26, 26–28, or ≥29) in FMR1 allele1 between POI cases whose ovarian function resumed and those whose ovarian function did not. It is suggested that the CGG repeat number in allele1, but not that in allele2 (longer allele), was significantly associated with POI occurrence (P < 0.001). Fewer than 26 or more than 28 CGG repeats in FMR1 allele1 were both risk factors of POI occurrence.

Histopathologic examination of the genital tract in rabbits treated once or twice with a slow-release deslorelin implant for reversible suppression of ovarian function

A total of 13 rabbits were treated with a subcutaneous deslorelin long-term release implant (4.7 mg) to study the effect on ovarian function and histologic features of the uterus. Seven rabbits (group 1) were implanted with a slow-release deslorelin implant before onset of puberty for 273 days as a part of a previous study. After resumption of ovarian function had been confirmed, they were implanted again at the age of 430 days. Six adult rabbits (>177 days old; group 2) were implanted with a slow-release deslorelin implant for 273 days. Ovarian function before, during, and after treatment with the implant was assessed by measuring serum progesterone levels 10 days after a challenge injection of a short-acting GnRH (0.8 μg buserelin intramuscularly) on progesterone levels in peripheral blood. Values more than 4 ng/mL progesterone were considered to verify ovarian function. Animals in group 1 underwent ovariohysterectomy during the second treatment with the implant and the uteri, and ovaries were subjected to histopathologic examination. Endometrial hyperplasia and endometritis were observed in 5 of 7 animals. Nonatretic and atretic follicles at different developmental stages, but no active corpora lutea, were present in the ovaries. Ovariohysterectomy of group 2 animals was performed 2 to 12 months after implant removal. The histopathologic examination of the uterus and ovary of four animals neutered during induced pseudopregnancy showed no signs of uterine disorders. In two animals undergoing ovariohysterectomy 12 months after implant removal, endometritis was present. Their ovaries contained follicles at different developmental stages and corpora albicantia. Reversible suppression of ovarian function can be achieved in female rabbits by the use of GnRH slow-release implants administered before or after puberty. The findings of endometrial hyperplasia and endometritis in seven out of 13 rabbits treated once or twice with the implant may indicate that the development of age-related pathologies of the uterus cannot be prevented by the suppression of ovarian function with a long-acting GnRH implant.

Long-term outcome of ovarian function in women with intermittent premature ovarian insufficiency.

Spontaneous resumption of ovarian function is not a rare phenomenon in patients with premature ovarian insufficiency (POI). The outcome of this resumption is not known. To describe the outcome following the resumption of ovarian function in POI patients. Cross-sectional study. University medical centre. Cumulative incidence of ovarian function resumption and risk factors arresting this resumption during follow-up were determined in a large cohort of POI women. Five hundred and seven patients were included in the study, with a follow-up of 3·44 ± 4·05 years (0-29). Of these, 117 (23%) had features of ovarian function resumption. The cumulative incidence of pregnancy was 3·5% among the whole cohort and 15·3% among patients with resumption of ovarian function. Fifty-five patients (47%) experienced an arrest of their resumption during the follow-up period. In univariate analysis, high FSH and DHEA levels at initial evaluation were risk factors for the arrest of the resumption of ovarian function. In multivariate analysis, high FSH levels at the initial evaluation [1·89 (1·10-3·23), P = 0·03] and older age at diagnosis [1·53 (1·01-2·33), P = 0·04] were risk factors for the arrest of this resumption. Resumption of ovarian function is not a rare or brief phenomenon in POI women. The identification of predictive factors of this resumption, as well as its duration, increases our knowledge of the natural history of POI, and will improve the medical management, especially infertility counselling of these patients.

Utility of gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a systematic review and meta-analysis.

BackgroundPremature ovarian failure and infertility following chemotherapy are major concerns for premenopausal women with breast cancer. A potential ovarian function preservation strategy is administration of gonadotropin-releasing hormone (GnRH) agonists during adjuvant chemotherapy; however, studies of the clinical efficacy of GnRH agonists to protect chemotherapy-induced ovarian damage have shown mixed results.ObjectiveThis meta-analysis study was designed to estimate the efficacy of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian damage in premenopausal women with breast cancer.MethodsElectronic literature databases (PubMed, EMBASE, MEDLINE, Cochrane Library databases searching, China National Knowledge Infrastructure, Web of Science, and the Wanfang Data) were searched for relevant randomized controlled trials (RCTs) published until September 2015. Only RCTs that examined the effect of GnRH agonists for chemotherapy-induced ovarian failure in premenopausal women with breast cancer were selected. The rate of spontaneous resumption of menses and spontaneous pregnancy were collected. All data were analyzed by RevMan 5.3 (Cochrane Collaboration, Copenhagen, Denmark) and Stata 12.0 (StataCorp, College Station, TX, USA).ResultsEleven RCTs with a total of 1,062 participants (GnRH agonists administered concurrently with chemotherapy, n=541; chemotherapy alone, n=521) were included in the meta-analysis. A significantly greater number of women treated with GnRH agonist experienced spontaneous resumption of menses after the adjuvant chemotherapy, yielding a pooled odds ratio of 2.57 (versus chemotherapy alone, 95% confidence interval (CI)=1.65, 4.01; P<0.0001). A subgroup analysis showed that addition of GnRH agonists significantly improved the resumption of menses rate in patients who were hormone-insensitive. However, the two treatment groups experienced similar spontaneous pregnancy (odds ratio =0.177; 95% CI=0.92, 1.40; P=0.09).ConclusionGnRH agonists cotreatment with chemotherapy in premenopausal women with breast cancer plays a beneficial role in resumption of ovarian function, with a higher rate of resumption of menses. However, treatment with GnRH agonists does not appear to exhibit its protective effects in fertility.

Protecting Ovaries During Chemotherapy Through Gonad Suppression

To estimate whether gonadotropin-releasing hormone (GnRH) analog administration during chemotherapy can protect against development of ovarian toxicity. MEDLINE (1966 to present), EMBASE (1980 to present), Cochrane Central Register of Controlled Trials (CENTRAL), World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were searched through March 2015 using the phrases: "gonadotropin-releasing hormone," "chemotherapy," and "premature ovarian failure." Hand-search on conference abstracts, SCOPUS, and ISI Web of Science were also searched. Published English-language randomized controlled trials comparing resumption of ovarian function between GnRH analogs plus chemotherapy with chemotherapy without GnRH analogs were included. Studies including women with pelvic metastases or recent history of receiving chemotherapy were excluded. Accordingly, 10 eligible trials (907 women) were analyzed. Our primary outcome was the proportion of women with resumed ovarian function (defined as resumption of menstruation, prevention of chemotherapy-induced ovarian failure, or both) at the longest follow-up after the end of chemotherapy. Secondary outcomes were evaluating ovarian reserve parameters and pregnancy. Risk ratio was used to integrate qualitative results and mean difference was used for quantitative data. Gonadotropin-releasing hormone analog cotreatment did not significantly increase ovarian function resumption (320/468 [68.4%] in GnRH analog arm and 263/439 [59.9%] in the chemotherapy alone arm; risk ratio 1.12, 95% confidence interval [CI] 0.99-1.27). No protective effect existed after subgroup analyses (type of malignancy [P=.31], age [P=.14], and GnRH analog type [P=.44]). Gonadotropin-releasing hormone analogs did not protect any of ovarian reserve parameters, whether follicle-stimulating hormone (mean difference -2.63, 95% CI -7.33 to 2.07), antral follicle count (mean difference 1.66, 95% CI -0.69 to 4.01), or anti-Müllerian hormone (mean difference 0.31, 95% CI -0.41 to 1.03). Spontaneous pregnancy was also comparable (risk ratio 1.63, 95% CI 0.94-2.82). Gonadotropin-releasing hormone analog administration during chemotherapy does not appear to protect the ovaries from gonadal toxicity. It is not a reliable method for fertility preservation.

Elevated progesterone levels in women on DHEA supplementation likely represent assay interference

Dear Editor, We read with interest the recent case report by Strauss et al. regarding a woman with diminished ovarian reserve who had higher serum progesterone levels after treatment with DHEA [1]. The authors clearly demonstrate that serum progesterone measurements increased while the patient was receiving DHEA supplementation after ovarian transplantation. The authors hypothesized that this progesterone must be derived from the adrenal glands. Another significant possibility exists. Data from our lab has demonstrated that increased progesterone levels seen after DHEA administration are likely due to cross-reactivity with the immunoassay and do not represent circulating progesterone. Our group and others have noted that when women were placed on DHEA, baseline serum progesterone levels were markedly higher than those measured prior to DHEA supplementation [2]. While other authors have assumed this indicated a true increase in progesterone production of either an ovarian or adrenal source, the possibility of assay interference must be considered. Much of the ingested DHEA is rapidly sulfated and converted to DHEA-SO4. We recently demonstrated [3] that the addition of pure DHEA-SO4 solutions (containing no progesterone) resulted in dose-dependent increases in progesterone assay results in spite of there being no additional progesterone in the samples . This phenomenon was demonstrated on three different commercially available immunoassay platforms. Thus, the elevated progesterone measured in this young woman post-ovarian transplant likely reflects the fact that she was properly taking her prescribed DHEA and the progesterone assay cross-reacted with her elevated serum DHEA-SO4. The implications of this assay interference go beyond monitoring of the resumption of ovarian function post transplantation. Given the importance of late follicular progesterone elevations on clinical outcomes after fresh embryo transfer [4], it is important for each clinical program that prescribes DHEA to quantify the level of interference with their progesterone assay and to consider those data when making clinical decisions.

Resumption of ovarian function after 4 years of estro-progestin treatment in a young woman with Crohn’s disease and premature ovarian insufficiency: a case report

To report the long-term management of a case of premature ovarian insufficiency of unknown origin in a young woman with Crohn's disease. Here is reported the case of a 20 years old woman with Crohn's disease presenting with two years amenorrhea and FSH and LH levels of 255 mIU/ml and 182 mIU/ml respectively, who received 10 months corticosteroid treatment followed by 7 years of estro-progestin treatment. Corticosteroid treatment was ineffective in restoring patients gonadotropin levels as well as ovarian volume, while estro-progestins promoted a prompt reduction in gonadotrophin levels, which returned in the normal range after two years of treatment, as well as restoration of ovarian function, which occurred after four years of estrogens administration, as demonstrated by normal ovarian volume and ovulatory follicles at ultrasound, and by the re-establishment of regular menses after estroprogestin discontinuation. Long-term suppression of the endogenous gonadotropins using estroprogestins may be suggested as a treatment able to restore ovarian responsiveness even in patients with premature ovarian insufficiency showing highly elevated gonadotropin levels.

Resumption of Ovarian Function and Pregnancies in 358 Patients With Premature Ovarian Failure

Context: Resumption of ovarian activity and spontaneous pregnancies are described in patients with premature ovarian failure (POF), but there is a lack of data concerning the prevalence of and predictive factors for these phenomena. Objective: The aim of the study was to determine both the prevalence of and predictive factors for spontaneous resumption of ovarian function in POF patients. Design and Setting: A mixed retrospective and prospective study was performed at a referral center for reproductive endocrinology. Patients: A total of 358 consecutive POF patients were followed from 1997 to 2010 in our center. Main Outcomes Measures: The cumulative incidence of resumption of ovarian function was determined, and predictive factors were identified by univariate and multivariate analysis. Results: Of 358 patients with idiopathic POF, 86 (24%) patients presented features indicating resumption of ovarian function, and in 77 cases (88%) within 1 yr of diagnosis. Twenty-one spontaneous pregnancies (16 births, ...

Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation

To describe the first live birth after transplantation of ovarian tissue following overnight transportation of the tissue before freezing. Technical note. University department of obstetrics and gynecology. A 25-year-old cancer survivor with previous Hodgkin disease and relapse. The ovarian tissue was kept cool for >20 hours in a special transport medium and a special cooling device before it was cryopreserved. After premature ovarian failure due to preconditioning chemotherapy for bone marrow transplantation, the cryopreserved ovarian tissue was transplanted orthotopically. Resumption of ovarian function after transplantation, recovery of fertility, and pregnancy. Ovarian function returned in the patient 3 months after transplantation, as shown by follicle development and estrogen production. During the fifth menstrual cycle, mild stimulation with FSH was initiated in accordance with a low-dose protocol. When ultrasonography revealed a follicle 18-20 mm in size in the ovarian graft, hCG was added and the patient had sexual intercourse at the optimal time point. On day 14 of the luteal phase, hCG concentration and vaginal echography confirmed a viable intrauterine pregnancy, which resulted in a healthy live birth. Overnight transportation of ovarian tissue appears to be possible in combination with appropriate transportation logistics. However, further investigations are needed before this procedure can be offered as a chance for women to preserve fertility independently of direct access to a tissue-processing bank.