Exogenous Gonadotropin Administration Research Articles

Excessive Exogenous Gonadotropins and Genetic and Pregnancy Outcomes After Euploidy Embryo Transfer

The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive. To evaluate the associations of different doses and durations of gonadotropins with embryonic genetic status and pregnancy outcomes after euploid embryo transfer in couples with infertility. This study was a post hoc analysis of a multicenter randomized clinical trial (RCT) conducted at 14 reproductive centers throughout China from July 2017 to June 2018 that evaluated the cumulative live birth rate with or without preimplantation genetic testing for aneuploidy (PGT-A) among couples with infertility and good prognosis. The PGT-A group from the original RCT was selected for secondary analysis. Patients were divided into 4 groups according to the total dosage of exogenous gonadotropins and treatment duration: group 1 (≤1500 IU and <10 days), group 2 (≤1500 IU and ≥10 days), group 3 (>1500 IU and <10 days), and group 4 (>1 500 IU and ≥10 days). Group 1 served as the control group. Data were analyzed from June through August 2023. Blastocyst biopsy and PGT-A. The primary outcomes were embryonic aneuploidy, embryonic mosaicism, and cumulative live birth rates after euploid embryo transfer. A total of 603 couples (mean [SD] age of prospective mothers, 29.13 [3.61] years) who underwent PGT-A were included, and 1809 embryos were screened using next-generation sequencing. The embryo mosaicism rate was significantly higher in groups 2 (44 of 339 embryos [13.0%]; adjusted odds ratio [aOR], 1.69 [95% CI, 1.09-2.64]), 3 (27 of 186 embryos [14.5%]; aOR, 1.98 [95% CI, 1.15-3.40]), and 4 (82 of 651 embryos [12.6%]; aOR, 1.60 [95% CI, 1.07-2.38]) than in group 1 (56 of 633 embryos [8.8%]). There were no associations between gonadotropin dosage or duration and the embryo aneuploidy rate. The cumulative live birth rate was significantly lower in groups 2 (83 of 113 couples [73.5%]; aOR, 0.49 [95% CI, 0.27-0.88]), 3 (42 of 62 couples [67.7%]; aOR, 0.41 [95% CI, 0.21-0.82]), and 4 (161 of 217 couples [74.2%]; aOR, 0.53 [95% CI, 0.31-0.89]) than in group 1 (180 of 211 couples [85.3%]). In this study, excessive exogenous gonadotropin administration was associated with increased embryonic mosaicism and decreased cumulative live birth rate after euploid embryo transfer in couples with a good prognosis. These findings suggest that consideration should be given to minimizing exogenous gonadotropin dosage and limiting treatment duration to improve embryo outcomes and increase the live birth rate. ClinicalTrials.gov Identifier: NCT03118141.

Lipid droplet synthesis is associated with angiogenesis in mouse ovarian follicles†.

Lipid droplets (LDs) are endoplasmic reticulum (ER)-derived organelles comprising a core of neutral lipids surrounded by a phospholipid monolayer. Lipid droplets play important roles in lipid metabolism and energy homeostasis. Mammalian ovaries have been hypothesized to use neutral lipids stored in LDs to produce the hormones and nutrients necessary for rapid follicular development; however, our understanding of LD synthesis remains incomplete. In this study, we generated transgenic reporter mice that express mCherry fused to HPos, a minimal peptide that localizes specifically to nascent LDs synthesized at the ER. With this tool for visualizing initial LD synthesis in ovaries, we found that LDs are synthesized continuously in theca cells but rarely in inner granulosa cells (Gc) during early follicular development. Administration of exogenous gonadotropin enhances LD synthesis in the Gc, suggesting that LD synthesis is hormonally regulated. In contrast, we observed copious LD synthesis in the corpus luteum, and excessive LDs accumulation in atretic follicles. Furthermore, we demonstrated that LD synthesis is synchronized with angiogenesis around the follicle and that suppressing angiogenesis caused defective LD biosynthesis in developing follicles. Overall, our study is the first to demonstrate a spatiotemporally regulated interplay between LD synthesis and neovascularization during mammalian follicular development.

Granulosa cell genes that regulate ovarian follicle development beyond the antral stage: The role of estrogen receptor β

Follicle development beyond the preantral stage is dependent on gonadotropins. FSH signaling is crucial for the advancement of preantral follicles to the antral stage, and LH signaling is essential for further maturation of preovulatory follicles. Estrogen is intricately tied to gonadotropin signaling during the advanced stages of folliculogenesis. We observed that Erβnull ovarian follicles fail to develop beyond the antral stage, even after exogenous gonadotropin stimulation. As ERβ is primarily expressed in the granulosa cells (GCs), we explored the gonadotropin-regulated GC genes that induce maturation of antral follicles. Synchronized follicle development was induced by administration of exogenous gonadotropins to wildtype 4-wk-old female rats. The GC transcriptome was analyzed via RNA-sequencing before and after gonadotropin stimulation. An Erβnull mutant model that fails to show follicle maturation was also included in order to identify the ERβ-regulated genes involved at this step. We observed that specific groups of genes were differentially expressed in response to PMSG or hCG administration in wildtype rats. While some of the PMSG or hCG-induced genes showed a similar expression pattern in Erβnull GCs, a subset of PMSG- or hCG-induced genes showed a differential expression pattern in Erβnull GCs. These latter ERβ-regulated genes included previously known FSH or LH target genes including Lhcgr, Cyp11a1, Cyp19a1, Pgr, Runx2, Egfr, Kiss1, and Ptgs2, which are involved in follicle development, oocyte maturation, and ovulation. We also identified novel ERβ-regulated genes including Jaml, Galnt6, Znf750, Dusp9, Wnt16, and Mageb16 that failed to respond to gonadotropin stimulation in Erβnull GCs. Our findings indicate that the gonadotropin-induced spatiotemporal pattern of gene expression is essential for ovarian follicle maturation beyond the antral stage. However, expression of a subset of those gonadotropin-induced genes is dependent on transcriptional regulation by ERβ.

Anti-M\xfcllerian hormone is correlated with cumulative live birth in minimal ovarian stimulation with clomiphene citrate: a retrospective cohort study

BackgroundSeveral studies have investigated the correlation between the serum anti-Müllerian hormone (AMH) level and in vitro fertilization (IVF) outcomes in controlled ovarian stimulation cycles; however, studies regarding the correlation of the serum AMH level with IVF outcomes in minimal ovarian stimulation cycles remain limited. In this study, we aimed to analyze the correlation of the serum AMH level with ovarian responsiveness, embryonic outcomes, and cumulative live birth rates in clomiphene citrate (CC)-based minimal ovarian stimulation cycles.MethodsClinical records of 689 women whose entire ovarian stimulation regimen consisted solely of minimal stimulation cycle IVF using CC alone from November 2017 to October 2019 were retrospectively reviewed. The association between IVF outcomes and the serum AMH level before the initiation of the first fertility treatment was analyzed. Furthermore, the correlation of the serum AMH level with cumulative live birth rates after IVF treatment was assessed. The Cochran-Armitage test, Pearson’s chi-squared test, Spearman rank correlation test, Student’s t-test, one-way analysis of variance, logistic regression analysis, Kaplan-Meier method and Cox proportional hazards model were used to analyze the data.ResultsThe serum AMH level positively correlated with the number of retrieved oocytes, blastocyst formation rate, blastocyst cryopreservation rate, and live birth rate per oocyte retrieval in CC-based minimal ovarian stimulation cycles without any exogenous gonadotropin administration. Furthermore, the cumulative live birth rate and treatment period required for conceiving were strongly associated with the serum AMH level at the initiation of fertility treatment.ConclusionsA low serum AMH level correlated with low ovarian responsiveness, impaired pre-implantation embryonic development, and decreased cumulative live birth rate in CC-based minimal ovarian stimulation cycles. Therefore, the cycle success rate would be predicted by measuring the serum AMH level in minimal ovarian stimulation with CC alone.

Effect of ovarian stimulation on the expression of piRNA pathway proteins.

PIWI-interacting RNAs (piRNAs) play an important role in gametogenesis, fertility and embryonic development. The current study investigated the effect of different doses of pregnant mare serum gonadotrophin/human chorionic gonadotrophin (PMSG/hCG) and repeated ovarian stimulation (OS) on the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9, qnd Mitopld genes, which have crucial roles in the biogenesis and function of piRNAs. Here, we found that after treatment with 7.5 I.U. PMSG/hCG and two repeated rounds of OS, both the mRNA and protein levels of Tdrd9, Tdrd1 and Mael showed the greatest decrease in the ovarian tissue, but the plasma E2 levels showed the strongest increases (p<0.05). However, we found that the Mitopld, Miwi and Mili gene levels were decreased significantly after treatment with 12.5 I.U. PMSG/hCG. Our results suggested that exogenous gonadotropin administration leads to a significant decrease in the expression of the Mili, Miwi, Mael, Tdrd1, Tdrd9 and Mitopld genes, which are critically important in the piRNA pathway, and the changes in the expression levels of Tdrd9, Tdrd1 and Mael may be associated with plasma E2 levels. New comprehensive studies are needed to reduce the potential effects of OS on the piRNA pathway, which silences transposable elements and maintains genome integrity, and to contribute to the safety of OS.

An Isolated Hypogonadotropic Hypogonadism due to a L102P Inactivating Mutation of KISS1R/GPR54 in a Large Family

KISS1R (GPR54) mutations have been reported in several patients with congenital normosmic idiopathic hypogonadotropic hypogonadism (nIHH). We aim to describe in detail nIHH patients with KISS1R (GPR54) mutations belonging to one related extended family and to review the literature. A homozygous mutation (T305C) leading to a leucine substitution with proline (L102P) was found in three affected kindred (2 males and 1 female) from a consanguineous Saudi Arabian family. This residue is localized within the first exoloop of the receptor, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs its function. In the affected female, a combined gonadotropin administration restored regular period and ovulation and she conceived with a healthy baby boy after 4 years of marriage. We showed that a loss-of-function mutation (p.Tyr305C) in the KISS1R gene can cause (L102P) KISS1 receptor dysfunction and familial nIHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of periods and later on pregnancy by an exogenous gonadotropin administration further support, in humans, that the KISS1R mutation has no other harmful effects on the patients apart from the gonadotropin secretion impairment.

Ovarian hyperstimulation syndrome leading to ventriculoperitoneal shunt malfunction: Case report

Ventriculoperitoneal shunt (VPS) insertion is a common neurosurgical procedure for hydrocephalus. Unfortunately, VPS malfunction is not uncommon, with an estimated cumulative rate of 32% at 5 years. As flow through the shunt is influenced by the pressure gradient between the ventricles and the peritoneal cavity, malfunction may be caused by elevated intra-abdominal pressure. We present a rare patient with ascites following ovarian hyperstimulation syndrome (OHSS) leading to shunt malfunction. OHSS is a potentially life-threatening complication of controlled ovarian stimulation caused by the administration of exogenous gonadotropins. In this patient clinical and radiological resolution of shunt dysfunction were achieved following peritoneocentesis. To our knowledge this is the first described case of OHSS leading to shunt malfunction, emphasizing the importance of awareness, early recognition and proper management of abdominal etiologies of VPS malfunction.

High level of C-type natriuretic peptide induced by hyperandrogen-mediated anovulation in polycystic ovary syndrome mice.

Polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, is a complex endocrinopathy that affects the fertility of 9-18% of reproductive-aged women. However, the exact mechanism of PCOS, especially hyperandrogen-induced anovulation, is largely unknown to date. Physiologically, the natriuretic peptide type C/natriuretic peptide receptor 2 (CNP/NPR2) system is essential for sustaining oocyte meiotic arrest until the preovulatory luteinizing hormone (LH) surge. We therefore hypothesized that the CNP/NPR2 system is also involved in PCOS and contributes to arresting oocyte meiosis and ovulation. Here, based on a dehydroepiandrosterone (DHEA)-induced PCOS-like mouse model, persistent high levels of CNP/NPR2 were detected in anovulation ovaries. Meanwhile, oocytes arrested at thegerminal vesicle stage correlated with persistent high levels of androgen and estrogen. We further showed that ovulation failure in these mice could be a result of elevated Nppc/Npr2 gene transcription that was directly increased by androgen (AR) and estrogen (ER) receptor signaling. Consistent with this, anovulation was alleviated by administration of either exogenous human chorionic gonadotropin (hCG) or inhibitors of AR or ER to reduce the level of CNP/NPR2. Additionally, the CNP/NPR2 expression pattern in the anovulated follicles was, to some extent, consistent with the clinical expression in PCOS patients. Therefore, our study highlights the important role an overactive CNP/NPR2 system caused by hyperandrogenism in preventing oocytes from maturation and ovulation in PCOS mice. Our findings provide insight into potential mechanisms responsible for infertility in women with PCOS.

Deficiency in DGCR8-dependent canonical microRNAs causes infertility due to multiple abnormalities during uterine development in mice.

DGCR8 is an RNA-binding protein that interacts with DROSHA to produce pre-microRNA in the nucleus, while DICER generates not only mature microRNA, but also endogenous small interfering RNAs in the cytoplasm. Here, we produced Dgcr8 conditional knock-out mice using progesterone receptor (PR)-Cre (Dgcr8d/d) and demonstrated that canonical microRNAs dependent on the DROSHA-DGCR8 complex are required for uterine development as well as female fertility in mice. Adult Dgcr8d/d females neither underwent regular reproductive cycles nor produced pups, whereas administration of exogenous gonadotropins induced normal ovulation in these mice. Interestingly, immune cells associated with acute inflammation aberrantly infiltrated into reproductive organs of pregnant Dgcr8d/d mice. Regarding uterine development, multiple uterine abnormalities were noticeable at 4 weeks of age when PR is significantly increased, and the severity of these deformities increased over time. Gland formation and myometrial layers were significantly reduced, and the stromal cell compartment did not expand and became atrophic during uterine development in these mice. These results were consistent with aberrantly reduced stromal cell proliferation and completely failed decidualization. Collectively, we suggest that DGCR8-dependent canonical microRNAs are essential for uterine development and physiological processes such as proper immune modulation, reproductive cycle, and steroid hormone responsiveness in mice.

Mole modifications following controlled ovarian stimulation for assisted reproduction technologies

The role of estrogens on moles biology remains undefined although estrogenic receptors have been found on melanocytes. It has been postulated that supraphysiological estrogen levels could promote the progression of moles to melanoma. Women undergoing controlled ovarian stimulation (COS) for assisted reproductive technologies (ART) are exposed to high levels of estrogens, produced by the ovary in response to exogenous gonadotropin administration. The aim of this study is to assess whether COS for ART may have an impact on mole structure and/or characteristics. Women undergoing to ART for various infertility conditions were included in the study. Personal and clinical data were collected. Dermatoscopic features and scores (total dermoscopy score--TDS) were statistically compared before COS and after a 6-month follow-up period. Statistical correlation was performed between estradiol, FSH blood levels and relative variation in moles dimensions. A total of 46 patients were included in the study. One hundred and seventy-five melanocytic lesions from 31 patients were evaluated at both time points. Although statistically significant differences were found in mole dimension and TDS between the two time points, these differences had no relevance in the clinical setting not suggesting the need for mole excision. Moreover, the only statistically significant correlation with estradiol blood concentration on hCG administration day was found with one-axis dimensional variation. To our knowledge this is the first work to evaluate the effect of COS on moles. The obtained results do not support a causal relation between the supraphysiological hormone levels stimulation and worsening of clinical and dermoscopical features of moles. Further study is needed to clarify whether estrogens plays a role in melanoma.

Gonadotropin-induced puberty does not impair reproductive performance of gilts over three parities.

The aim of this study was to evaluate the reproductive performance of three parities of gilts treated or not treated with gonadotropin to induce puberty. Sixty gilts received 600 IU of equine chorionic gonadotropin (eCG) followed by 2.5 mg of porcine luteinizing hormone (LH) 72 h later. Fifty-nine other gilts were exposed only to a mature boar for 15 min twice daily. Artificial insemination (AI) was performed at 0, 12 and 24 h after the detection of oestrus, and gestation was confirmed by ultrasound after 35 days. Sows were inseminated at the first post-weaning oestrus. The total numbers of piglets born, piglets born alive, stillborn, mummified foetuses, as well as pregnancy and farrowing rates were evaluated for each of the three parities. Culling rates, farrowing intervals and weaning-to-oestrous intervals (WEI) were also analysed. Mean age at puberty and oestrous manifestation were not significantly different between treatments (p = 0.0639; 179.20 ± 17.52 compared with 173.96 ± 16.94, 91.66% compared with 94.92%) across the experimental period. However, females that underwent puberty induction showed modest increases both in the number of total pigs born and in the number of piglets born alive. In conclusion, puberty induction through exogenous gonadotropin administration in field conditions did not induce a more concentrated first oestrous manifestation, but trended to a modest increase in the number of pigs born alive in the first parity and a reduced culling rate during the first gestation.

Fertility preservation in breast cancer patients.

Breast cancer is the most common malignant tumor in women of reproductive age, and is characterized by a high survival rate owing to improved antineoplastic treatments. Young survivors face the prospect of a diminished fertility as a consequence of the gonadotoxic chemotherapy, and many are seeking ways to preserve their fertility. Embryo and/or oocyte cryopreservation following controlled ovarian stimulation is currently the fertility preservation method of choice, but breast cancer patients may have contraindications to exogenous gonadotropin administration and may not have enough time to undergo ovarian stimulation prior to chemotherapy. Fortunately, many other options are available for these women, such as the letrozole-follicle-stimulating hormone ovarian stimulation protocol, in vitro maturation of oocytes and ovarian tissue cryopreservation. In this review, we discuss the benefits and disadvantages of the different fertility preservation techniques that can be offered to breast cancer patients.

Maturation in vitro des ovocytes en préservation de la fertilité féminine

Recovering immature oocytes from unstimulated ovaries, followed by in vitro maturation (IVM) was initially proposed to avoid the risks and side effects of exogenous gonadotropin administration. Therefore, during the past decades, IVM was mainly offered to patients with polycystic ovary syndrome at high risk of ovarian hyperstimulation syndrome. However, the development of fertility preservation has recently opened new perspectives in the field of IVM. The present review reports the possible indications of IVM, in the strategy of female fertility preservation.

Natriuretic peptide precursor C delays meiotic resumption and sustains gap junction-mediated communication in bovine cumulus-enclosed oocytes.

Oocyte in vitro maturation (IVM) has become a valuable technological tool for animal breeding and cloning and the treatment of human infertility because it does not require the administration of exogenous gonadotropin to obtain fertilizable oocytes. However, embryo development after IVM is lower compared to in vivo maturation, most likely because oocytes collected for IVM are heterogeneous with respect to their developmental competencies. Attempts to improve IVM outcome have relied upon either prematuration culture (PMC) or two-step maturation strategies in the hope of normalizing variations in developmental competence. Such culture systems invoke the pharmacological arrest of meiosis, in theory providing oocytes sufficient time to complete the acquisition of developmental competence after cumulus-enclosed oocytes isolation from the follicle. The present study was designed to test the efficiency of natriuretic peptide precursor C (NPPC) as a nonpharmacologic meiosis-arresting agent during IVM in a monoovulatory species. NPPC has been shown to maintain meiotic arrest in vivo and in vitro in mice and pigs; however, the use of this molecule for PMC has yet to have been explored. Toward this end, meiotic cell cycle reentry, gap-junction functionality, and chromatin configuration changes were investigated in bovine cumulus-enclosed oocytes cultured in the presence of NPPC. Moreover, oocyte developmental competence was investigated after IVM, in vitro fertilization, and embryo culture and compared to standard IVM-in vitro fertilization protocol without PMC. Our results suggest that NPPC can be used to delay meiotic resumption and increase the developmental competence of bovine oocytes when used in PMC protocols.

Involvement of hyaluronan synthesis in ovarian follicle growth in rats

Most of the previous studies on ovarian hyaluronan (HA) have focused on mature antral follicles or corpora lutea, but scarcely on small preantral follicles. Moreover, the origin of follicular HA is unknown. To clarify the localization of HA and its synthases in small growing follicles, involvement of HA in follicle growth, and gonadotropin regulation of HA synthase (Has) gene expression, in this study, perinatal, immature, and adult ovaries of Wistar-Imamichi rats were examined histologically and biochemically and by in vitro follicle culture. HA was detected in the extracellular matrix of granulosa and theca cell layers of primary follicles and more advanced follicles. Ovarian HA accumulation ontogenetically started in the sex cords of perinatal rats, and its primary site shifted to the intrafollicular region of primary follicles within 5 days of birth. The Has1-3 mRNAs were expressed in the ovaries of perinatal, prepubertal, and adult rats, and the expression levels of Has1 and Has2 genes were modulated during the estrous cycle in adult rats and following administration of exogenous gonadotropins in immature acyclic rats. The Has1 and Has2 mRNAs were predominantly localized in the theca and granulosa cell layers of growing follicles respectively. Treatments with chemicals known to reduce ovarian HA synthesis induced follicular atresia. More directly, the addition of Streptomyces hyaluronidase, which specifically degrades HA, induced the arrest of follicle growth in an in vitro culture system. These results indicate that gonadotropin-regulated HA synthesis is involved in normal follicle growth.

New Trends in Female Fertility Preservation: In Vitro Maturation of Oocytes

As antineoplastic treatments have become more successful, an increasing number of women with cancer survive to endure the long-term consequences of chemotherapy. One of the most important of these consequences in young females is premature ovarian failure and infertility. Owing to increasing survival rates, many of these young women are seeking methods to preserve their fertility. Currently, embryo/oocyte cryopreservation obtained after controlled ovarian stimulation appears to provide the best fertility preservation option. However, patients may not have enough time to undergo ovarian stimulation prior to chemotherapy and/or have contraindications to exogenous gonadotropin administration owing to estrogen-dependant tumors. In vitro maturation of oocytes is an attractive alternative for fertility preservation in cancer patients because it does not require ovarian stimulation and it can be performed at any time of the menstrual cycle. In addition, this technique can be combined with ovarian tissue cryobanking. In this review, we discuss the position of in vitro maturation of oocytes in the fertility preservation strategy in young women.

Successful pregnancy following low-dose hCG administration in addition to hMG in a patient with hypothalamic amenorrhea due to weight loss

We describe successful ovulation induction with low-dose hCG administration in addition to hMG in a patient with refractory hypothalamic amenorrhea. A 24-year-old woman with weight loss-related amenorrhea underwent ovulation induction and intracytoplasmic sperm injection (ICSI). Administration of exogenous gonadotropins was ineffective in ovulation induction. Supplementation with low-dose hCG in order to increase luteinizing hormone (LH) activity in the late follicular phase produced late folliculogenesis and steroidogenesis, and ovulation was then successfully induced. This report reacknowledges the critical role that LH plays cooperatively with follicle-stimulating hormone in both folliculogenesis and steroidogenesis.

The reproducibility of serum anti-Müllerian hormone in subfertile women: within and between patient variability

Serum anti-Müllerian hormone concentrations vary significantly over time and this should be taken into account when tailoring treatment protocols for patients undergoing controlled ovarian hyperstimulation (COH). Compared with FSH, serum anti-Müllerian hormone may have greater discriminatory power because of its modest intrapatient variation and the larger interpatient variation.

Ablation of the Sam68 gene impairs female fertility and gonadotropin-dependent follicle development

Sam68 is a multifunctional RNA-binding protein highly expressed in the gonads, whose ablation causes male infertility. Herein, we have investigated Sam68 expression in the adult ovary and its function in female fertility. Immunohistochemistry showed that Sam68 was localized in the nucleus of oocytes and follicular cells at all stages of folliculogenesis. Sam68(-/-) females were severely subfertile, and they showed a delay in the age of first pregnancy, increased breeding time for successful pregnancy and yielded smaller litters. Morphological analyses indicated a significant reduction in the number of secondary and pre-antral follicles in the ovary. These defects were associated with alteration of oestrous cycles and a reduced number of ovulated oocytes, which were only partially restored by the administration of exogenous gonadotropins. Crosslinking/immunoprecipitation experiments showed that Sam68 directly binds the mRNAs for the follicle-stimulating hormone (FSH) and the luteinizing hormone receptors (Fshr and Lhcgr), which were downregulated in ovaries of adult knockout females. Stimulation of immature females with FSH-like pregnant mare serum gonadotropin (PMSG), or of follicular cells with the FSH second messenger analogue 8Br-cAMP, caused the upregulation of Sam68. The increase in Sam68 levels paralleled that of the Fshr and Lhcgr mRNAs in the pre-ovulatory follicle and was required to allow accumulation of these transcripts in follicular cells. These studies identify a new crucial function for Sam68 in the regulation of female fertility and indicate that this protein is required to insure proper expression of the gonadotropin receptor transcripts in pre-ovulatory follicles in adult ovary.

Ovarian stimulation retards postimplantation development and alters global gene expression profile of blastocysts in mouse

This study compares the quality, developmental capacity and global gene expression profile of embryos generated from superovulated and natural cycles. We found that ovarian stimulation impaired quality of blastocysts (cell number: 68.9 +/- 6.9 vs. 76.8 +/- 7.9; diameter of blastocysts: 145.3 +/- 76.9 microm vs. 152.6 +/- 65.5 microm), fetus development (rate of development to term: 45.5% vs. 69.1%; weight of 18.5-dpc fetuses: 1.23 +/- 0.03 g vs. 1.34 +/- 0.03 g) and caused 92 genes differentially expressed.