Gonadotropin Treatment Research Articles

Proliferation Profile of Uterine Endometrial Stromal Cells during In Vitro Culture with Gonadotropins: Recombinant versus Urinary Follicle Stimulating Hormone.

Provision of optimal endometrial stromal cells is essential in uterine tissue engineering. Culture of these cells is significantly influenced by gonadotropin hormones. This investigation attempted to define the proliferation profiles of murine uterine endometrial stromal cells during in vitro culture with recombinant follicle stimulating hormone (rFSH), urinary follicle stimulating hormone (uFSH), and human chorionic gonadotropin (hCG). Murine uterine endometrial stromal cells were collected from 8-week-old mice and cultured in vitro up to 72h, with rFSH, uFSH, or hCG. Cell cycles were analyzed by BrdU assay, and cyclin D1 expression was evaluated according to dose and duration of gonadotropin treatment. BrdU assay showed a further inhibitory effect on murine uterine endometrial stromal cell proliferation when cultured with rFSH compared to uFSH, and a similar inhibitory proliferation profile when cultured with hCG at a specific range of concentrations. The expression of cyclin D1 of murine uterine endometrial stromal cells was down-regulated when cultured with rFSH, uFSH, or hCG, compared to control. FSH may inhibit the proliferation of murine uterine endometrial stromal cells during in vitro culture. rFSH may have more significant inhibitory effects on the proliferation of endometrial stromal cells than uFSH. Establishing an optimal endocrine milieu is necessary using more advanced combination of female hormones for in vitro culture of this type of cells.

Effect of equine chorionic gonadotropin treatment during a progesterone-based timed artificial insemination program on reproductive performance in seasonal-calving lactating dairy cows

The aim of this study was to investigate the effect of progesterone (P4)-based timed artificial insemination (TAI) programs on fertility in seasonal-calving, pasture-based dairy herds. A total of 1,421 lactating dairy cows on 4 spring-calving farms were stratified based on days in milk (DIM) and parity and randomly allocated to 1 of 3 treatments: (1) control: no hormonal treatment; cows inseminated at detected estrus; (2) P4-Ovsynch: cows received a 7-d P4-releasing intravaginal device (PRID Delta; CEVA Santé Animale, Libourne, France) with 100 μg of a gonadotropin-releasing hormone (GnRH) analog (Ovarelin; CEVA Santé Animale) at PRID insertion, a 25-mg injection of PGF2α (Enzaprost; CEVA Santé Animale) at PRID removal, GnRH at 56 h after device removal and TAI 16 h later; (3) P4-Ovsynch+eCG: the same as P4-Ovsynch, but cows received 500 IU of equine chorionic gonadotropin (eCG; Syncrostim; CEVA Santé Animale) at PRID removal. At 10 d before mating start date (MSD), all cows that were ≥35 DIM were examined by transrectal ultrasound to assess presence or absence of a corpus luteum; body condition score (BCS) was also recorded. Pregnancy diagnosis was performed by transrectal ultrasonography 30 to 35 d after insemination. Overall pregnancy/AI (P/AI) was not different between groups (50.9, 49.8, and 46.3% for control, P4-Ovsynch, and P4-Ovsynch+eCG, respectively) but the 21-d pregnancy rate was increased by the use of synchronization (35.0, 51.7, and 47.2%, respectively). Compared with the control group, synchronization significantly reduced the interval from MSD to conception (34.6, 23.0, and 26.5 d, respectively) and consequently reduced the average days open (98.0, 86.0, and 89.0 d). Across all treatment groups, DIM at the start of synchronization affected P/AI (42.3, 49.5, and 53.9% for <60, 60-80, and >80 DIM, respectively), but neither parity (46.5, 50.4, and 48.4% for parity 1, 2, and ≥3, respectively) nor BCS (44.0, 49.4, and 58.6% for ≤2.50, 2.75-3.25, and ≥3.50, respectively) affected the likelihood of P/AI. Two-way interactions between treatment and DIM, parity, or BCS were not detected. In conclusion, the use of TAI accelerated pregnancy establishment in cows in a pasture-based system by reducing days open, but eCG administration at PRID removal did not affect P/AI.

The Evolution of Assisted Reproductive Technologies: A Modern Approach to Ovarian Stimulation

In celebration of the 40th anniversary of the first in vitro fertilisation (IVF) baby this year, the symposium focussed on the modern-day approach to ovarian stimulation (OS). Chairperson Prof Fauser welcomed delegates with a look at the key achievements related to OS in the context of assisted reproductive technologies (ART) over the past century. Treatments have evolved from the first crude preparations to the refined gonadotrophin products available for clinical use today. The theme of personalisation in OS was introduced by Dr Labarta, who looked at how we can use accurate biomarker measurements to assess ovarian reserve, predict ovarian response, and, therefore, personalise treatment accordingly. Of the biomarkers currently available, anti-Müllerian hormone (AMH) has been identified as the best tool for individualised gonadotrophin dosing. AMH can also be used to drive evidence-based decisions in the choice of gonadotrophin treatment. Dr Alper presented results from the MEGASET HR trial, which investigated highly purified human menopausal gonadotrophin (HP-hMG) in patients identified via their AMH levels as potential high responders. Dr Havelock then demonstrated how AMH, along with body weight, has allowed for the development of the first dosing algorithm for tailoring treatment with follitropin delta, which has been validated in randomised controlled trials (RCT). Finally, the symposium closed with Prof Fauser concluding that, using the biomarker AMH, it is now possible to personalise not only the dose of gonadotrophin but also the choice of gonadotrophin treatment, representing important first steps in truly individualising OS.

A Comparison of Efficacy Of Aromatase Inhibitors (Letrozole), Clomiphene Citrate And Recombinant F.S.H In Induction Of Ovulation In Polycystic Overian Syndrome

Background: Polycystic ovarian syndrome is also called hyper-androgenic anovulation syndrome.It is a set of symptoms due to elevated male hormone in women. The major features of PCOS include menstrual dysfunction, anovulation and signs of hyperandrogens Other signs and symptoms of PCOS include hirsutism, infertility, obesity, metabolic syndrome, diabetes and obstructive sleep apnea. On examination, finding in women with PCOS may include virilizing signs, acanthosis nigricans, hypertension and enlarged ovaries (may or may not present).Ovulation induction in women with PCOS suffering from anovulatory infertility includes the use of antioestrogen, insulin sensitisers, aromatase inhibitors (Letrozole), gonadotropin (FSH) and surgical treatment. Objective: The present study aimed at comparing between the efficacy of aromatase inhibitors(letrizole), clomiphene citrate and recombinant (FSH) on induction of ovulation in polycystic ovarian syndrome. Patients and Methods: the present study was conducted on 150 patients with polycystic ovarian syndrome according to the Rotterdam criteria for polycystic ovarian syndrome with history of menstrual disturbance and whose age ranged between 18-37 years. In the current study, patients were allocated into 3 equal groups: group A (Clomiphene citrate), group B (Letrizole) and group C (Recombinant FSH). Results: Clomiphene citrate, letrizole and recombinant (FSH)were the common to be used for induction of ovulation in polycystic ovarian syndrome.In our study we proved that recombinant (FSH) is the most effective of these drugs,followed by letrizole and the least is clomiphene citrate. Conclusion: PCOS is a major cause of infertility in women.Medical treatment (induction of ovulation) is one of the major methods of management of PCOS. Recombinant (FSH) has the higest efficacy in our study.

A Comparison of Efficacy Of Aromatase Inhibitors (Letrozole), Clomiphene Citrate And Recombinant F.S.H In Induction Of Ovulation In Polycystic Overian Syndrome

Background: Polycystic ovarian syndrome is also called hyper-androgenic anovulation syndrome.It is a set of symptoms due to elevated male hormone in women. The major features of PCOS include menstrual dysfunction, anovulation and signs of hyperandrogens Other signs and symptoms of PCOS include hirsutism, infertility, obesity, metabolic syndrome, diabetes and obstructive sleep apnea. On examination, finding in women with PCOS may include virilizing signs, acanthosis nigricans, hypertension and enlarged ovaries (may or may not present).Ovulation induction in women with PCOS suffering from anovulatory infertility includes the use of antioestrogen, insulin sensitisers, aromatase inhibitors (Letrozole), gonadotropin (FSH) and surgical treatment. Objective: The present study aimed at comparing between the efficacy of aromatase inhibitors(letrizole), clomiphene citrate and recombinant (FSH) on induction of ovulation in polycystic ovarian syndrome. Patients and Methods: the present study was conducted on 150 patients with polycystic ovarian syndrome according to the Rotterdam criteria for polycystic ovarian syndrome with history of menstrual disturbance and whose age ranged between 18-37 years. In the current study, patients were allocated into 3 equal groups: group A (Clomiphene citrate), group B (Letrizole) and group C (Recombinant FSH). Results: Clomiphene citrate, letrizole and recombinant (FSH)were the common to be used for induction of ovulation in polycystic ovarian syndrome.In our study we proved that recombinant (FSH) is the most effective of these drugs,followed by letrizole and the least is clomiphene citrate. Conclusion: PCOS is a major cause of infertility in women.Medical treatment (induction of ovulation) is one of the major methods of management of PCOS. Recombinant (FSH) has the higest efficacy in our study.

Human chorionic gonadotropin induces decidualization of ectopic human endometrium more effectively than forskolin in an in-vivo endometriosis model.

Endometriosis, characterized by the presence of endometrial tissue at ectopic sites, is a leading cause of pelvic pain and subfertility in women. The stromal compartment of the endometrium is considered to play a pivotal role in the establishment and persistence of endometriotic lesions, thus impaired decidualization of these cells may result in enhanced invasion capacity at ectopic sites. Consequently, stimulation of decidualization may alleviate this disease. To analyze the effect of systemically applied compounds on decidualization of ectopic endometrial tissue, endometriosis was induced by suturing human eutopic endometrium to the peritoneum of 22 NOD/SCID mice. Each mouse received four tissue fragments from the same patient. Mice were randomly allocated either to one control and three experimental groups ( n = 4/group) which were treated with progesterone alone or in combination with forskolin or human chorionic gonadotropin for seven days or to one control and one experimental group ( n = 3/group) which was treated with progesterone and human chorionic gonadotropin for 10 days followed by 7 days without treatment. At the end of the experiments, lesions were measured and analyzed for markers of decidualization (FOXO-1, prolactin) and proliferation (Ki-67). Decidualization was induced in the ectopic lesions by systemic treatment in vivo. This induction was significantly stronger after treatment with progesterone in combination with human chorionic gonadotropin than with forskolin or with progesterone alone. Only the combination with human chorionic gonadotropin led to induction of FOXO1 protein expression and a significant physiologic transformation of the ectopic endometrial stromal cells after seven days of treatment. After termination of human chorionic gonadotropin treatment, the decidualization process continued, leading to a significant inhibition of proliferation. Thus, decidualization of human ectopic endometrial tissue can be induced in a humanized endometriosis mouse model in vivo. This model may help to decipher the signal pathways involved in this decidualization process and to develop novel therapeutical approaches to alleviate this painful disease. Impact statement Impaired decidualization of endometrial stromal cells may contribute to the development of endometriosis, and an increased decidualization reaction may prevent or alleviate this prevalent gynecological disease. Human chorionic gonadotropin (hCG) has been shown to promote decidualization in eutopic endometrium. Up to now in vitro studies mainly used cAMP for successful induction of decidualization of isolated endometrial stromal cells. Here, for the first time, decidualization of ectopic endometrial lesions is induced in an experimental endometriosis mouse model, comparing the effectiveness of hCG with that of the direct adenylyl cyclase activator Forskolin. In this 3D-organ structure in vivo, hCG proved to be more effective in the induction of decidualization than forskolin. Particularly in case of progesterone resistance, alternative pathways inducing decidualization could alleviate endometriosis, and the sophisticated hCG action could constitute a therapeutical tool to induce terminal differentiation in ectopic endometrial lesions.

Outcomes of random start versus clomiphene citrate and gonadotropin cycles in occult premature ovarian insufficiency patients, refusing oocyte donation: a retrospective cohort study

The aim of this study is to present the clinical outcomes of a random start, a spontaneous folliculogenesis protocol versus Clomiphene Citrate and Gonadotropin treatment in women with occult premature ovarian insufficiency. Women underwent treatment between 1 February 2009, and 30 May 2016. 41 women were treated with the random start protocol while 48 cases received ovarian stimulation with clomiphene and gonadotropins. All included cases met the criteria of 4 months of oligo-ovulation, follicular-stimulating hormone levels over 30 IU/L and anti-Mullerian hormone levels below 0.30 ng/mL. The random start protocol involved following the subjects for up to 6 months until spontaneous folliculogenesis occurred. The mean number of oocytes collected, mature oocytes, fertilized oocytes, and grade II embryos were significantly higher in the random start protocol (p < .05). The doses of gonadotropin administration and hCG were significantly lower in the random start protocol (p < .05). The clinical pregnancy and live birth rates were significantly higher in the random start protocol (p < .05). Likely stimulation is of little benefit in women with occult premature ovarian insufficiency. Observation while waiting for spontaneous folliculogenesis results in better outcomes, and less oocyte collections.

Anti-Müllerian hormone and Oestradiol as markers of future reproductive success in juvenile gilts

There is a need for an early marker for reproductive success in gilts as the traditional process for selecting breeding females is inefficient. There is evidence that circulating anti-Müllerian hormone (AMH) is indicative of ovarian reserve, antral follicle populations, gonadotropin responsiveness and fertility in various species other than the pig. Additionally, oestradiol (E2) has been shown to mark antral follicle populations in cattle and pregnancy outcomes in women, after gonadotropin treatment. The aims of this study were to determine whether 1) serum levels of AMH or E2, prior to or after gonadotropin injection at 60, 80 or 100 days of age, and 2) hormonal changes in response to gonadotropin stimulation (i.e. declining, plateauing or increasing hormone levels), are associated with future reproductive success in juvenile gilts. Serum samples were obtained at 0, 2 and 4 days after injection and mating and litter data were collected until parity three. Results showed that, regardless of age group and parity, Day 0 E2 levels were positively associated with the probability of stillbirth (P = 0.035) and E2 levels on Day 0 (P = 0.032), Day 2 (P = 0.045) and Day 4 (P = 0.019) were negatively associated with the number of piglets born alive. Further, both a single measurement of serum AMH levels at Day 2 (P = 0.048) and the AMH response type were associated with gestation length (P = 0.012). These findings suggest that serum AMH and E2 levels can be used to inform the selection of gilts for the breeding herd.

Effects of subcutaneous melatonin implants and short-term intravaginal progestagen treatments on estrus induction and fertility of Kivircik ewes on seasonal anestrus.

The aim of this study was to compare the efficacy of estrus induction and fertility by using subcutaneous melatonin (MEL, T1) and short-term intravaginal medroxyprogesteronacetate plus pregnant mare serum gonadotropin treatments (sMAP+eCG, T2) in ewes on seasonaly anestrus. In this study, 105 mature clinically healthy Kivircik ewes in anestrus season and 4 rams were used. After synchronization applications, ewes exhibiting estrus signs were hand-mated with rams known to be fertile. Blood samples were collected at different times in order to determine progesterone (P4) concentrations. Results showed that estrus manipulation protocols induced significant improvement in pregnancy rate. All the fertility results obtained with the sMAP+eCG or MEL groups were similar, in seasonal anestrus. The efficacy duration of P4 in the MEL group was longer than that in short-term progestagen group. Plasma P4 concentrations was significantly different between the first (I) and last (III) measurement days (p0.01). Increase in P4 concentration in T2 group was faster than that in T1 group, and blood P4 concentrations at higher levels could successfully be achieved by using any of the protocols in this study during the seasonal anestrus. In conclusion, according to the results obtained, the hormone application groups received very high estrus response. In addition, the twin ratio was found to be higher in T1 group compared to those determined in the other groups (T2 and Control group). Furthermore, plasma P4 concentrations and high birth rates were obtained in ewes in T1 and T2 groups. These procedures can be considered a good alternative to traditional procedures due to its flexibility under field conditions.

MP07-16 CONCOMITANT TESTOSTERONE BASED ON HCG TREATMENT RESULTED IN EARLIER MASCULINIZATION AND NO INFERIOR SPERMATOGENESIS COMPARED TO HCG ALONE IN TREATMENT OF IHH PATIENTS

You have accessJournal of UrologyInfertility: Therapy II1 Apr 2018MP07-16 CONCOMITANT TESTOSTERONE BASED ON HCG TREATMENT RESULTED IN EARLIER MASCULINIZATION AND NO INFERIOR SPERMATOGENESIS COMPARED TO HCG ALONE IN TREATMENT OF IHH PATIENTS Yinwei Chen, Yonghua Niu, Hao Xu, Daoqi Wang, Hongyang Jiang, Gaurab Pokhrel, Tao Wang, Shaogang Wang, and Jihong Liu Yinwei ChenYinwei Chen More articles by this author , Yonghua NiuYonghua Niu More articles by this author , Hao XuHao Xu More articles by this author , Daoqi WangDaoqi Wang More articles by this author , Hongyang JiangHongyang Jiang More articles by this author , Gaurab PokhrelGaurab Pokhrel More articles by this author , Tao WangTao Wang More articles by this author , Shaogang WangShaogang Wang More articles by this author , and Jihong LiuJihong Liu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3079AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The primary goal in treatment of idiopathic hypogonadotropic hypogonadism (IHH) is to induce masculinization and spermatogenesis. Exogeneous testosterone (T) can induce masculinization but not spermatogenesis and rather may be associated with impaired spermatogenesis. This retrospective study aims to determine whether concomitant T based on HCG treatment show significantly harmful impacts on spermatogenesis in IHH patients compared HCG alone. METHODS A total of 107 male IHH patients were recruited and were divided into group A (n=54) and group B (n=53) according to their choices. The study protocol was approved by the ethics committee of Huazhong University of Science and Technology. Group A received intramuscular dose of HCG, while group B received HCG combined with testosterone undecanoate (TU). In both groups, HCG was injected with initial dosage of 2000IU twice weekly. Group B received additional 40mg oral dose of TU twice daily. Patients were regularly followed up and their HCG dosages were adjusted to maintain serum T in the normal range at each visit. SPSS version 23.0 was used to for data analysis and the Tanner stage, testicular volumes, hormone levels, semen parameters and side effects were compared between the two groups. RESULTS The median follow-up time was 31.3 months. Significant improvements were seen in Tanner stages, testicular volumes, hormone levels and semen parameters in both groups between pre- and post-treatment period (P < 0.001). Compared to the group A, the median time to achieve Pubic hair Tanner stage III, V and genital Tanner stage III, V was significantly shorter in group B (P < 0.05), and its median time to achieve normal T was also significantly shorter (P < 0.001). But there were no significant differences in terms of testicular volume and sperm concentration. The median time to achieve spermatogenesis, sperm concentration =15×106/ml and progressive motility rate = 32% showed no remarkable differences between the two groups. In addition, group B showed no significant side effects, especially in terms of gynecomastia. CONCLUSIONS Concomitant T based on HCG treatment was associated with earlier masculinization and no adverse effect on spermatogenesis compared to HCG alone, which suggested that it may be a good alternative treatment option for IHH patients, especially promoting development of confidence and build better compliance during initial stage of gonadotropin treatment probably. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e94 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Yinwei Chen More articles by this author Yonghua Niu More articles by this author Hao Xu More articles by this author Daoqi Wang More articles by this author Hongyang Jiang More articles by this author Gaurab Pokhrel More articles by this author Tao Wang More articles by this author Shaogang Wang More articles by this author Jihong Liu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Superovulation Affects the Gene Expression Patterns of Mice Oocytes and Preimplantation Embryos Produced by Different Assisted Reproductive Technologies

Objectives: In this experiment, possible effect of superovulation on important molecular profiles of oocytes and embryos were examined in mice regarding their development. Materials and Methods: A total of 120 metaphase II oocytes were produced by super or spontaneous ovulation. Blastocyst-stage embryos were produced after in vitro fertilization (IVF) and in vivo fertilization. Blastocysts that have been obtained from naturally mated female without gonadotrophin treatment were also used as controls. Using real-time polymerase chain reaction (PCR), the mRNA expression patterns of Bone morphogenesis protein (Bmp 15(, hepatoma-derived growth factor (Hdgf), DNA methyl transpherase-1 (Dnmt-1), developmental pluripotency associated 3 (Dppa3), and zinc finger protein 57 (Zfp57) genes were compared between superovulated and spontaneously ovulated oocytes; the expression patterns of H19 and small nuclear ribonucleoprotein N) Snrpn( imprinting genes between embryos produced from these oocytes were also compared. Results: The results of the study showed that expression of five maternal effect genes (Bmp15, Hdgf, Dnmt-1, Dppa3, and Zfp57) in superovulated oocytes were significantly reduced (P<0.05). However, the rates of cleavage to the blastocyst stages were not significantly different (P<0.05) between superovulated and naturally ovulated oocytes in cultured embryos. Moreover, superovulation disturbed the expression patterns of imprinting genes (H19 and Snrpn) in single blastocysts obtained by different assisted reproductive techniques (ARTs). Conclusions: The findings indicated that superovulation affected the molecular characteristics of ART conceived embryos.

Low-dose gonadotropin induction of ovulation in anovulatory women: still needed in the age of IVF.

Low-dose, step-up gonadotropin is the treatment of choice for women with polycystic ovary syndrome (PCOS) who have not conceived after anti-oestrogen treatment and as an effective alternative to pulsatile GnRH in women with hypogonadotropic hypogonadism (HH). There has been, however, no large-scale, comparative study between the two groups using low-dose gonadotropins. Here, we performed a retrospective, comparative analysis, in a single clinic database, of efficacy and safety of induction of ovulation using low-dose gonadotropins in 364 women with PCOS and 80 women with HH. The rate of ovulation was high in both PCOS (83%) and HH (84%) but mono-follicular, ovulatory cycles were more prevalent in PCOS than in HH (77% vs 53%, P < 0.0001) and the proportion of cycles that were abandoned was higher in HH than in PCOS (25% vs 15%, P < 0.0001). The median threshold dose of gonadotropin required to induce ovulation was 75 IU/day in PCOS and 113 IU/day in HH (P < 0.001) and the range of doses was greater in HH women. Forty-nine percent of women with PCOS and 65% of those with HH conceived (more than 90% within 6 cycles of treatment) and had at least one pregnancy. Multiple pregnancies (all twins) occurred in only 4% of women with PCOS and 5% of those with HH. These findings emphasise the efficacy and safety of low-dose gonadotropin treatment for both clomiphene-resistant women with PCOS and those with HH. These results highlight the importance of choosing the more physiological approach of gonadotropin induction of ovulation in both groups as the most appropriate treatment, in preference to IVF.

Overexpression of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in boys with cryptorchidism.

BackgroundThe ubiquitin-proteasome system regulate p53, caspase and Bcl-2 family proteins, and is crucial for the degradation of the defective germ cells in testes. Purpose: to evaluate the concentration of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in the blood plasma of boys with cryptorchidism and if there is any correlation with patient age.MethodsPatients—50 boys aged 1–4 years (median = 2,4y.) with unilateral cryptorchidism. Exclusion criteria were: previous human chorionic gonadotropin treatment, an abnormal karyotype, endocrine or immunological disorders or any long-term medication. The control group—50 healthy, age matched boys (aged 1–4 years, median = 2,1y.), admitted to the Pediatric Surgery Department for planned herniotomy. To investigate UCHL1 in blood plasma of boys with cryptorchidism, we used a novel technique Surface PLASMON RESONANCE Imaging (SPRI).ResultsThe median concentration of UCHL1 in the blood plasma of boys with cryptorchidism, was 5-folds higher than in boys with inguinal hernia, whose testicles were located in the scrotum. We also noticed statistically significant difference between UCHL1 levels in boys with cryptorchidism up to 2 years old, and above 2 years old. Older boys, whose testicles since birth were located in the inguinal pouch or in the abdominal cavity, had higher concentration of UCHL1 in their blood plasma, than boys from younger group. In the group of cryptorchid boys, we also found slightly lower concentrations of INSL3, without statistical significance and no correlation with UCHL1 levels.ConclusionsUchl1 concentrations in the blood plasma of boys with cryptorchidism, may reflect the heat-induced apoptosis of germ cells. Higher UCHL1 concentrations in older boys with undescended testicles, probably express intensity of germ cell apoptosis, more extensive when testicles are subjected to heat-stress for longer period. Further analyses of UCHL1 may help to elucidate its role in mechanisms influencing spermatogenesis.

The use of multiple ovulation, embryo cryopreservation and embryo transfer techniques to facilitate movement of genetic material between countries

The objective of the study was to evaluate the use multiple ovulation and embryo transfer techniques in an indigenous Greek dairy breed of sheep. We stimulated selected donor ewes of the Karagouniko breed to produce large numbers of embryos after the induction of multiple ovulations by gonadotropin treatment (superovulatory response). A total of 50 Greek Karagouniko ewes were synchronised into oestrus using progestagen pessaries and superovulated for embryo transfer using ovine FSH. Six days following laparoscopic insemination with fresh semen ewes were flushed surgically and embryos collected. Subsequently, the embryo recovery, along with embryo cryopreservation, embryo survival and quality were assessed. The Karagouniko donor ewes achieved a mean ovulation rate of 11.9 (SE. 0.89). The ova Recovery rate was 80,9% and 87,6% of the ova recovered being fertilised. A total of 327 (77,5%) of the viable embryos were assessed as being of sufficient quality for cryopreservation. The embryos ranged from late morulae to expanded blastocyst and were frozen via a 3-step process in 1.5 M ethylene glycol following repeated washing and trypsination. Cryopreserved embryos were frozen and then transported to Scotland, UK. There, embryos were thawed rapidly and re-hydrated via a 2 step sucrose/ethylene glycol gradient. A total of 92.4% of embryos frozen remained suitable for transfer semi-surgically into synchronized Scottish Blackface ewes. 183 embryos were transferred in total with a 66.1% survival rate. The survival rate of frozen thawed blastocysts(75%) was significantly greater than (P&lt;0.01) that for morulae (48%). It was concluded that MOET could be successfully applied in Greek dairy breeds of sheep as a means for genetic improvement. Frozenembryos could be a successful medium for the transportation of ovine genetic material from and to Greece, however, most likely the choice of embryonic stage for cryopreservation is crucial.

Effects of human chorionic gonadotropin treatment after artificial inseminations on conception rate with the first follicular wave dominant follicle in the ovary ipsilateral to the corpus luteum in lactating dairy cows

We examined the effect of human chorionic gonadotropin (hCG) treatment 5 days after artificial insemination (AI) on conception rate when the first-wave dominant follicle (DF) in the ovaries was either ipsilateral or contralateral to the corpus luteum (CL) in lactating dairy cows. 577 cows from 4 dairy farms were divided into the following two groups 5 days after AI using transrectal ultrasonography: (1) the ipsilateral group (IG; n = 348), in which the DF was ipsilateral to the CL, and (2) the contralateral group (CG; n = 229), in which the DF was contralateral to the CL. IG and CG were further subdivided into two groups: non-treatment groups, which received no treatment (IG, n = 220; CG, n = 128), and hCG treatment group, that was administrated 1500 IU hCG 5 days after AI (IG, n = 143; CG, n = 86). Pregnancy was diagnosed by rectal palpation or transrectal ultrasonography from 53 to 67 days after AI. Conception rate was significantly (P < 0.01) higher in the hCG treatment group of IG (40.6%) than in the non-treatment group of IG (21.4%); however, there was no difference in the non-treatment (51.7%) and hCG treatment (43.0%) groups of CG. Parity, farm, days in milk at AI, interaction between the farm and hCG treatment and interaction between the farm and location of the first-wave DF and CL did not affect conception rate. Our results suggest that conception rate can be improved by administrating hCG only to cows with the first wave DF ipsilateral to the CL.

The Effects of In Vitro Maturation Technique on The Expression of Genes Involved in Embryonic Genome Activation of Human Embryos.

Objective In vitro maturation technique (IVM) is shown to have an effect on full maturation of immature oocytes and the subsequent embryo development. Embryonic genome activation (EGA) is considered as a crucial and the first process after fertilization. EGA failure leads to embryo arrest and possible implantation failure. This study aimed to determine the role of IVM in EGA-related genes expression in human embryo originated from immature oocytes and recovered from women receiving gonadotrophin treatment for assisted reproduction. Materials and Methods In this experimental study, germinal vesicle (GV) oocytes were cultured in vitro. After intracytoplasmic sperm injection of the oocytes, fertilization, cleavage and embryo quality score were assessed in vitro and in vivo. After 3-4 days, a single blastomere was biopsied from the embryos and then frozen. Afterwards, the expression of EGA-related genes in embryos was assayed using quantitative reverse transcriptase-polymerase chain reaction (PCR). Results The in vitro study showed reduced quality of embryos. No significant difference was found between embryo quality scores for the two groups (P=0.754). The in vitro group exhibited a relatively reduced expression of the EGA- related genes, when compared to the in vivo group (all of them showed P=0.0001). ConclusionAlthough displaying the normal morphology, the IVM process appeared to have a negative influence on developmental gene expression levels of human preimplanted embryos. Based on our results, the embryo normal morphology cannot be considered as an ideal scale for the successful growth of embryo at implantation and downstream processes.

Laparoskopik Ovaryan Drilling: Klomifen Sitrata Dirençli Polikistik Over Sendromu Hastalarında İkinci Basamak Tedavide Gonadotropin Tedavisine Güvenli Bir Alternatif midir?

Laparoskopik Ovaryan Drilling: Klomifen Sitrata Dirençli Polikistik Over Sendromu Hastalarında İkinci Basamak Tedavide Gonadotropin Tedavisine Güvenli Bir Alternatif midir?

Evaluation of Prolidase Activity, Oxidative Stress, and Antioxidant Enzyme Levels in Testicular and Penile Tissues after Human Chorionic Gonadotropin Treatment in Rats by Predicting Infertility and Erectile Dysfunction

Objectives: Prolidase plays a vital role in collagen turnover, matrix remodeling, and cell growth. We aimed to evaluate the association between treatment with chorionic gonadotropin and infertility and erectile dysfunction by investigating tissue prolidase activity, oxidative stress, and levels of antioxidant enzymes. Materials and Methods: The 16 male Wistar albino rats used in this study were randomly divided into 2 groups: rats treated with human chorionic gonadotropin (hCG) and control rats (n = 8 in each group). The rats in the hCG group were subcutaneously injected with 50 IU hCG daily for 15 days, while the rats in the control group were subcutaneously injected isotonic saline. All of the rats were sacrificed by a lethal overdose of sodium pentobarbital at the first month after hCG administration. Prolidase activity and levels of malonyl aldehyde, glutathione reductase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were estimated in the testicular and penile tissue. The testicles and penis were transversely dissected and placed in formalin. Results: Levels of prolidase and malonyl aldehyde in the testicular and penile tissues were significantly higher in the hCG group than in the control group (p < 0.001), while levels of glutathione reductase, SOD, GSH-Px, and CAT were significantly lower in the hCG group than in the control group (p < 0.001). Conclusions: In this study, we observed that treatment with hCG increased prolidase activity and oxidative stress and decreased the antioxidant capacity of penile and testicular tissues; therefore, this may affect fertility and erectile function.

Cost-Effectiveness Analysis of the Gonadotropin Treatments HP-hMG and rFSH for Assisted Reproductive Technology in France: A Markov Model Analysis.

The objectives of this study were to assess (1) the expected cost of a live birth (LB) after in vitro fertilization with two different gonadotropin treatments [high purified human menopausal gonadotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH)] as the single cost variable, and (2) the cost effectiveness of HP-hMG relative to rFSH in the context of the routine practice of assisted reproductive technology (ART) in France. A Markov model was developed to simulate the therapeutic management, the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) courses, and the effects of complications in hypothetical cohorts of 30,000 patients undergoing IVF/ICSI with fresh embryo transfer (up to four attempts) using data from the MERIT and MEGASET clinical trials or from French routine ART practice. The cost per LB was estimated at €12,145 and at €14,247 with HP-hMG and rFSH, respectively, using efficacy data from published clinical trials. The resulting incremental cost-effectiveness ratio (ICER) was -€11,616 per LB. HP-hMG was less expensive by around €15.0 million and more effective by 1289 additional LBs. Using French clinical data, the cost per LB was €16,415 and €18,7531 with HP-hMG and rFSH, respectively. The ICER for HP-hMG versus rFSH was estimated at -€7,719 per LB with a saving of about €8.54 million and 1097 additional LBs. Deterministic sensitivity analyses showed that the main ICER drivers were the LB rate, followed by the total gonadotropin doses. The probabilistic sensitivity analysis indicated that HP-hMG was the dominant strategy in 71.2% of cases using the clinical trial data and in 50.2% of cases using the French data. This analysis indicates that compared with rFSH, HP-hMG is less costly for IVF/ICSI management from the French healthcare payer's viewpoint. The results of the present Markov model analysis are consistent with previous findings in other European countries.

Neonatal outcomes and congenital malformations in children born after human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles.

To investigate neonatal outcomes and congenital malformations in children born after in vitro fertilization (IVF) and vitrified embryo transfer cycles using human menopausal gonadotrophin and medroxyprogesterone acetate (hMG+MPA) treatment. We performed a retrospective cohort study including 4596 live born babies. During January 2014-June 2016, children born after either hMG+MPA treatment, gonadotropin releasing hormone agonist short protocol, or mild ovarian stimulation were included. The main outcome measures were neonatal outcomes and congenital malformations. Neonatal outcomes both for singletons and twins such as mean birth weight and length, gestational age, the frequency of preterm birth were comparable between groups. Rate of stillbirth and perinatal death were also similar. No significant differences were found in the overall incidence of congenital malformations between the three groups. Multivariable logistic regression indicated that hMG+MPA regimen did not significantly increase the risk of congenital malformations compared with short protocol and mild ovarian stimulation, with adjusted odds ratio of 1.22 [95% confidence interval (CI) 0.61-2.44] and 1.38 (CI 0.65-2.93), respectively, after adjusting for confounding factors. Our data suggested that compared with conventional ovarian stimulations, hMG+MPA treatment neither compromised neonatal outcomes of IVF newborns, nor did increase the prevalence of congenital malformations.