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Reproductive Biology and Endocrinology... Jan 2014Luteinizing hormone (LH) activity in human menopausal gonadotropin (hMG) preparations is derived from human chorionic gonadotropin (hCG) rather than LH. Therefore, we... (Comparative Study)
Comparative Study Observational Study
BACKGROUND
Luteinizing hormone (LH) activity in human menopausal gonadotropin (hMG) preparations is derived from human chorionic gonadotropin (hCG) rather than LH. Therefore, we aimed to determine whether there are similarities in the endocrine and follicular profiles of serum and follicular fluid from controlled ovarian stimulation with the recombinant gonadotropins follicle-stimulating hormone plus luteinizing hormone (rFSH + rLH) or highly purified human menopausal gonadotropin (HP-hMG).
METHODS
We performed a prospective observational study with 50 oocyte donors that received either a combination of recombinant gonadotropins (rFSH + rLH) or a mixture of urinary gonadotropins (HP-hMG) plus purified urinary FSH (uFSH). Results were analyzed using Student's t-test to compare continuous variables and the chi-squared test to compare proportions. P-values < 0.05 were considered statistically significant.
RESULTS
Although more oocytes were retrieved after treatment with recombinant than urinary gonadotropins (16.5 vs. 11.8; P = 0.049), a higher proportion of metaphase II ova (71.2% vs. 80.6%; P = 0.003) were obtained using urinary gonadotropins. On day 6 and on the day of triggering, serum steroid hormone levels were slightly but not significantly elevated in the recombinant group compared with the urinary group. In follicular fluid, no statistical differences were observed for intra-follicular levels of steroid hormones between the two protocols; ongoing pregnancy rates were similar (46.1% vs. 46.1%).
CONCLUSIONS
Our data suggest that endocrinological and follicular profiles do not differ between rFSH + rLH and HP-hMG stimulation.
Topics: Adult; Chorionic Gonadotropin; Endocrine System; Feasibility Studies; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Oocyte Donation; Pilot Projects; Pregnancy; Pregnancy Rate; Prospective Studies; Recombinant Proteins; Young Adult
PubMed: 24476504
DOI: 10.1186/1477-7827-12-10 -
Reproductive Biology and Endocrinology... Dec 2013Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles... (Observational Study)
Observational Study
The influence of circulating anti-Müllerian hormone on ovarian responsiveness to ovulation induction with gonadotrophins in women with polycystic ovarian syndrome: a pilot study.
BACKGROUND
Women with polycystic ovarian syndrome (PCOS) are known to have elevated circulating Anti-Müllerian hormone (AMH), which has been found to desensitize ovarian follicles to follicle stimulating hormone (FSH). The purpose of this study was to investigate the impact of high circulating AMH on ovarian responsiveness to ovulation induction with gonadotrophins in PCOS women.
METHODS
This prospective observational pilot study was conducted in two collaborating Fertility Centres in the UK and Egypt. The study included 20 consecutive anovulatory women with PCOS who underwent 34 cycles of human menopausal gonadotrophin (hMG) ovarian stimulation using chronic low-dose step up protocol. Blood samples were collected for the measurement of serum AMH concentrations in the early follicular (day 2-3) phase in all cycles of hMG treatment. The serum levels of AMH were compared between cycles with good vs. poor response. The good response rates and the total dose and duration of hMG treatment were compared between cycles with high vs. low serum AMH concentrations.
RESULTS
Cycles with poor response (no or delayed ovulation requiring >20 days of hMG treatment) had significantly (p = .007) higher median{range} serum AMH concentration (6.5{3.2-13.4}ng/ml) compared to that (4.0{2.2-10.2}ng/ml) of cycles with good response (ovulation within 20 days of hMG treatment). ROC curve showed AMH to be a useful predictor of poor response to hMG stimulation (AUC, 0.772; P = 0.007). Using a cut-off level of 4.7 ng/ml, AMH had a sensitivity of 100% and specificity of 58% in predicting poor response. The good response rate was significantly (p < .001) greater in cycles with lower AMH (<4.7 ng/ml) compared to that in those with AMH > = 4.7 ng/ml (100% vs. 35%, respectively). All cycles with markedly raised serum AMH levels (> 10.2 ng/ml) were associated with poor response. Cycles with high AMH (> = 4.7 ng/ml) required significantly (p < .001) greater amounts (median {range}, 1087{450-1650}IU) and longer duration (20 {12-30}days) of hMG stimulation than cycles with lower AMH (525 {225-900}IU and 8{6-14}days).
CONCLUSIONS
PCOS women with markedly raised circulating AMH seem to be resistant to hMG ovulation induction and may require a higher starting dose.
Topics: Anti-Mullerian Hormone; Biomarkers; Female; Humans; Infertility, Female; Menotropins; Ovulation Induction; Pilot Projects; Polycystic Ovary Syndrome; Treatment Outcome
PubMed: 24341292
DOI: 10.1186/1477-7827-11-115 -
Fertility and Sterility Nov 2013To assess follicular development after long-term xenotransplantation and exogenous stimulation of cryopreserved prepubertal ovarian tissue.
OBJECTIVE
To assess follicular development after long-term xenotransplantation and exogenous stimulation of cryopreserved prepubertal ovarian tissue.
DESIGN
Pilot study.
SETTING
Gynecology research unit in a university hospital.
PATIENT(S)
Cryopreserved ovarian fragments were obtained from five prepubertal patients aged 7.2-12.2 years.
INTERVENTION(S)
Xenografting of frozen-thawed prepubertal ovarian fragments to SCID mice for 5 months and exogenous stimulation.
MAIN OUTCOME MEASURE(S)
Follicular density, morphology, proliferation, development.
RESULT(S)
Follicular density varied between 1.05 and 47.89 follicles/mm(2) in frozen-thawed ovarian tissue and 0.48 and 32.74 follicles/mm(2) in grafted prepubertal ovarian tissue. Growing follicles at the last stage of follicular development were observed at significantly higher proportions after grafting. No statistical difference was evidenced in the number of primordial follicles, representing the largest proportion of the follicle pool (99.51% before grafting and 92.46% after grafting). Ki67 and antimüllerian hormone expression were observed in these growing follicles.
CONCLUSION(S)
This is the first description of transplantation of human cryopreserved prepubertal ovarian tissue to mice, demonstrating that a very high number of follicles survive after transplantation and a large pool of primordial follicles remains dormant. Growing follicles were observed, proving the responsiveness of prepubertal ovarian tissue to gonadotropins.
Topics: Animals; Anti-Mullerian Hormone; Biomarkers; Cell Proliferation; Child; Cryopreservation; Female; Fertility Agents, Female; Graft Survival; Hospitals, University; Humans; Ki-67 Antigen; Menotropins; Mice; Mice, SCID; Ovarian Follicle; Pilot Projects; Time Factors; Transplantation, Heterologous
PubMed: 23953325
DOI: 10.1016/j.fertnstert.2013.07.202 -
BMJ Open Jun 2013Poor response to ovarian stimulation affects a significant proportion of infertile couples undergoing in vitro fertilisation (IVF) treatment. Recently, the European...
BACKGROUND
Poor response to ovarian stimulation affects a significant proportion of infertile couples undergoing in vitro fertilisation (IVF) treatment. Recently, the European Society of Human Reproduction and Embryology developed new criteria to define poor ovarian response, the so-called Bologna criteria. Although preliminary studies in these patients demonstrated very low pregnancy rates, a recent pilot study has shown promising results in women <40 years old fulfilling the criteria, after treatment with corifollitropin α followed by highly purified menotropin (hpHMG) in a gonadotropin-releasing hormone (GnRH) antagonist setting. Corifollitropin α followed by menotropin for poor ovarian responders' trial (COMPORT) is a randomised trial aiming to investigate whether this novel protocol is superior to treatment with recombinant follicle-stimulating hormone (FSH) in an antagonist setting for young poor responders.
METHODS/DESIGN
COMPORT is a multicentre, open label, phase III randomised trial using a parallel two-arm design. 150 patients <40 years old fulfilling the 'Bologna criteria' will be randomised to corifollitropin α followed by hpHMG (group A) or recombinant FSH (group B) in a GnRH antagonist protocol for IVF/intracytoplasmic sperm injection (ICSI). The primary outcome is the ongoing pregnancy rate (defined as the presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation). Secondary outcomes are clinical and biochemical pregnancy rates and number of oocytes retrieved. Central randomisation will be performed using a computer-generated list and allocation concealment will be secured with the use of sealed-opaque envelopes. A sample size of 150 women is essential to detect a difference of 19.5% in ongoing pregnancy rates between group A (28%) and group B (8.5%) with a power of 85% and a level of significance at 0.05 using a two-sided Fisher's exact test.
PubMed: 23794545
DOI: 10.1136/bmjopen-2013-002938 -
Reproductive Sciences (Thousand Oaks,... Aug 2013Gonadotropins including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play a crucial role in human-assisted reproduction techniques. Despite wide use... (Comparative Study)
Comparative Study
Gonadotropins including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play a crucial role in human-assisted reproduction techniques. Despite wide use of recombinant gonadotropins in clinical practice, the efficacy of urinary gonadotropins and the dosage of LH component have not yet been elucidated. This study was designed to investigate the difference of follicle culture outcomes according to various compositions of gonadotropins during in vitro culture of mouse preantral follicles. Ovaries were obtained from the 14-day-old C57BL/6 mice, and preantral follicles were isolated and cultured in culture media supplemented with human menopausal gonadotropin (hMG) 200 mIU/mL (group 1), recombinant FSH and LH (rFSH + rLH) 200 mIU/mL each (group 2), rFSH 200 mIU/mL + rLH 100 mIU/mL (group 3), or rFSH 200 mIU/mL + rLH 20 mIU/mL (group 4). Follicle survival rate was significantly lower in group 4. Antral follicles in lower doses of LH (groups 3, 4) showed a statistically significant larger diameter and tended to have a higher antral formation rate. However, follicles in group 1 tended to have a higher oocyte maturation rate. Estradiol concentration from conditioned media from 2:1 FSH/LH (group 3) was significantly higher than those from 1:1 FSH/LH (group 2) or 10:1 FSH/LH (group 4). Half dose of rLH to rFSH facilitated upregulation of growth differentiation factor 9 (Gdf9) expression in granulosa cells when compared to 1:1 FSH/LH or 10:1 FSH/LH. Conclusively, recombinant gonadotropins provided a comparable condition to hMG, and half dose of rLH to rFSH seems to be more suitable for follicular development during in vitro culture.
Topics: Animals; Culture Media, Conditioned; Dose-Response Relationship, Drug; Estradiol; Female; Follicle Stimulating Hormone; Gene Expression Regulation; Granulosa Cells; Humans; In Vitro Oocyte Maturation Techniques; Luteinizing Hormone; Menotropins; Mice; Mice, Inbred C57BL; Ovarian Follicle; Recombinant Proteins; Tissue Culture Techniques
PubMed: 23239820
DOI: 10.1177/1933719112468948 -
Acta Obstetricia Et Gynecologica... Nov 2012To assess the psychological impact (Hospital Anxiety and Depression Scale) of an investigational ovarian stimulation protocol in women with premature ovarian failure... (Clinical Trial)
Clinical Trial
OBJECTIVE
To assess the psychological impact (Hospital Anxiety and Depression Scale) of an investigational ovarian stimulation protocol in women with premature ovarian failure (POF).
DESIGN
Prospective longitudinal study.
POPULATION
Ten women with POF.
METHODS
Women with idiopathic POF were placed on three consecutive treatment cycles consisting of gonadotropin ovarian stimulation after estrogen priming, gonadotropin-releasing hormone agonist pituitary desensitization, and corticosteroid immune suppression.
RESULTS
Median anxiety and depression scores increased significantly from baseline following three consecutive treatment cycles from 4.0 (range 2.0-8.0) to 11.0 (range 10.0-14.0) (p-value 0.041) and from 1.5 (range 0-6.0) to 9.0 (range 7.0-10.0) (p-value 0.039), respectively. There were nine "probable" anxiety (90%) and three "probable" depression (30%) cases on the final treatment cycle compared with none (0%) on baseline (p-value 0.004 and 0.250, respectively).
CONCLUSIONS
The use of investigational ovarian stimulation protocols in women with idiopathic POF was associated with excessive psychological strain. Women with POF should be cautioned against the potentially harmful aspect of similar treatments of unproven benefit.
Topics: Adolescent; Adult; Anxiety; Buserelin; Chorionic Gonadotropin; Depression; Estrogens; Estrogens, Conjugated (USP); Female; Glucocorticoids; Humans; Infertility, Female; Insemination, Artificial; Longitudinal Studies; Medroxyprogesterone Acetate; Menotropins; Ovary; Ovulation Induction; Prednisone; Primary Ovarian Insufficiency; Prospective Studies; Psychiatric Status Rating Scales; Reproductive Control Agents; Ultrasonography; Young Adult
PubMed: 22994379
DOI: 10.1111/aogs.12004 -
Gynecological Endocrinology : the... Jan 2013The aim of this retrospective study was to investigate the impact of endogenous and exogenous luteinizing hormone (LH) activity on treatment outcome, when taking into...
Live-birth rates after HP-hMG stimulation in the long GnRH agonist protocol: association with mid-follicular hCG and progesterone concentrations, but not with LH concentrations.
The aim of this retrospective study was to investigate the impact of endogenous and exogenous luteinizing hormone (LH) activity on treatment outcome, when taking into consideration potential confounding variables. Data were derived from IVF patients (n = 358) stimulated with highly purified menotrophin (HP-hMG) in a long gonadotrophin-releasing hormone (GnRH) agonist protocol. Simple retrospective logistic regression analysis showed that the mid-follicular exogenous concentrations of human chorionic gonadotrophin (hCG) (p = 0.027), provided by the HP-hMG preparation, and female age (p = 0.009) were significantly associated with live-birth rate, while the mid-follicular progesterone concentration (p = 0.075), the estradiol concentration on last stimulation day (p = 0.075) and number of embryos transferred (p = 0.071) were borderline significant. Endogenous LH was not associated with live-birth rate; neither at start of stimulation (p = 0.123), nor in the mid-follicular phase (p = 0.933) or on the last day of stimulation (p = 0.589). In the multiple regression analysis of life birth, mid-follicular hCG (p = 0.016) was identified as a positive predictor, and age (p = 0.004) and mid-follicular progesterone (p = 0.029) as negative predictors. In conclusion, mid-follicular concentrations of exogenous hCG and progesterone, but not endogenous LH, are associated with live-birth rate in IVF patients treated with HP-hMG in a long GnRH agonist cycle.
Topics: Adult; Chorionic Gonadotropin; Female; Fertility Agents, Female; Fertilization in Vitro; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Logistic Models; Luteinizing Hormone; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Retrospective Studies; Young Adult
PubMed: 22809021
DOI: 10.3109/09513590.2012.705379 -
Taiwanese Journal of Obstetrics &... Jun 2012
Successful pregnancy in a woman with Kallmann's syndrome using human menopausal gonadotropin followed by low-dose human chorionic gonadotropin in the mid-to-late follicular phase.
Topics: Adult; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Follicular Phase; Humans; Infertility, Female; Kallmann Syndrome; Menotropins; Ovulation Induction; Pregnancy; Pregnancy, Twin
PubMed: 22795116
DOI: 10.1016/j.tjog.2012.04.027 -
Reproductive Biology and Endocrinology... Jun 2012We here report the first investigation of exclusively elective in vitro fertilization (IVF) cycles in women with no apparent history of infertility. Since IVF outcome in... (Comparative Study)
Comparative Study
BACKGROUND
We here report the first investigation of exclusively elective in vitro fertilization (IVF) cycles in women with no apparent history of infertility. Since IVF outcome in women with infertility are always influenced by underlying causes of infertility, a study on non-infertile women may offer new insights.
METHODS
We investigated 88 females without history of infertility in 109 consecutive elective IVF cycles, almost exclusively performed for purposes of preimplantation genetic screening (PGS; i.e., elective gender selection). The following questions were addressed: (i) impact of PGS on IVF pregnancy chances; (ii) impact of transfer of 1 vs. ≥2 embryos on IVF pregnancy chances; (iii) correlation of anti-Müllerian hormone (AMH) levels to embryo ploidy (iv) effect of gonadotropin dosage used in stimulation on available embryos for transfer; and (v) in form of a 1:1 case control study, compared 33 elective PGS cycles with matched control cycles without PGS, performed in couples with either prior tubal ligations and/or severe male factor infertility as indication of IVF.
RESULTS
The overall clinical pregnancy rate for the group was 36.7%; pregnancy was associated with number of euploid (P = 0.009) and number of embryos transferred (P = 0.001). Odds of pregnancy were 3.4-times higher if ≥4 euploid embryos were produced in comparison to <4 (95% CI 1.2 to 9.2; P = 0.019), and odds of pregnancy were 6.6-times higher if greater than or equal to 2 rather than <1 euploid embryos were transferred (95% CI 2.0 to 21.7; P = 0.002). Increasing AMH (P = 0.001) and gonadotropin dosage used in ovarian stimulation (P = 0.024), was, independently, associated with number of available euploid embryos. Increasing AMH, but not follicle stimulating hormone (FSH), was associated with number of embryos available for biopsy and PGS (P = 0.0001). Implantation rates were 26.4% with PGS and 9.5% without (P = 0.008). Women undergoing PGS, demonstrated 4.58-times higher odds of pregnancy than matched controls (95% CI 1.102 to 19.060, Exp 4.584, P = 0.036).
CONCLUSIONS
This study suggests that outcomes of elective IVF cycles may significantly deviate from infertility-associated cycles. Affirming proof of concept for PGS, utilizing day-3 embryo biopsy and fluorescence in-situ hybridization (FISH), both widely held responsible for earlier failures to establish such proof, suggests that the principal cause of prior failures were likely not insufficient laboratory techniques but poor patient selection for PGS. Such a conclusion questions the current reintroduction of PGS with improved techniques and technologies in absence of prior determination of suited patient populations.
Topics: Adult; Anti-Mullerian Hormone; Embryo Transfer; Embryo, Mammalian; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Infertility, Female; Male; Menotropins; Ploidies; Pregnancy; Pregnancy Rate; Preimplantation Diagnosis; Sex Preselection; Single Embryo Transfer; Treatment Outcome
PubMed: 22716082
DOI: 10.1186/1477-7827-10-48 -
Iranian Biomedical Journal 2012To achieve multiple oocytes for in vitro fertilization, ovulation induction is induced by gonadotropins; however, it has several effects on oocytes and embryo quality...
BACKGROUND
To achieve multiple oocytes for in vitro fertilization, ovulation induction is induced by gonadotropins; however, it has several effects on oocytes and embryo quality and endometrium receptivity. The aim of this study was to assess ultrastructural changes of corpus luteum after ovarian induction using human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) during luteal phase at implantation period.
METHODS
Female NMRI mice (6-8 weeks) were divided into control and stimulated groups. In the control group, the mice were rendered pseudopregnant and in the ovarian induction group, the mice were rendered pseudopregnant after the ovarian induction. The samples were obtained from the ovary in each group at the same time during luteal phase at implantation period. Ultrastructural changes were assessed using electron microscopy study.
RESULTS
Our results displayed some identifiable changes in ultrastructure of corpus luteum in ovarian induction group. These changes included enhancement of the apoptosis and intercellular space, whereas the angiogenesis was decreased. The findings indicated a decline in organelle density in the cytoplasm of ovarian induction, such as mitochondria, endoplasmic reticulum and polyribosome. Furthermore, chromatin condensation of nuclei was observed in some cells.
CONCLUSION
The ovarian induction using HMG and HCG resulted in some ultrastructural changes on the corpus luteum at implantation period, which could affect on the pregnancy rate.
Topics: Animals; Apoptosis; Cell Nucleus; Chorionic Gonadotropin; Chromatin; Corpus Luteum; Embryo Implantation; Endoplasmic Reticulum; Female; Luteal Phase; Menotropins; Mice; Mice, Inbred Strains; Mitochondria; Neovascularization, Physiologic; Ovulation Induction; Polyribosomes; Pseudopregnancy; Random Allocation
PubMed: 22562030
DOI: 10.6091/ibj.1033.2012