-
Fertility and Sterility Aug 2016To study whether intranasal GnRH agonist (GnRHa) can be effectively used for luteal support in high-responder patients undergoing fresh-embryo transfer after ovulation...
Intranasal gonadotropin-releasing hormone agonist (GnRHa) for luteal-phase support following GnRHa triggering, a novel approach to avoid ovarian hyperstimulation syndrome in high responders.
OBJECTIVE
To study whether intranasal GnRH agonist (GnRHa) can be effectively used for luteal support in high-responder patients undergoing fresh-embryo transfer after ovulation induction with the use of GnRHa.
DESIGN
Retrospective cohort study.
SETTING
Private fertility clinic.
PATIENT(S)
Forty-six high-responder patients were administered a GnRHa ovulation trigger to avoid ovarian hyperstimulation syndrome (OHSS), followed by 2 weeks of daily intranasal GnRHa (nafarelin) for luteal-phase support. No additional progesterone supplementation was administrated.
INTERVENTION(S)
Intranasal GnRHa for luteal-phase support.
MAIN OUTCOME MEASURE(S)
The primary outcome was ongoing clinical pregnancy rate.
RESULT(S)
High median progesterone levels were measured at midluteal phase and on the day of the first positive pregnancy test (190 nmol/L on both measures). We obtained 24 (52.1%) ongoing clinical pregnancies. None of the patients developed OHSS.
CONCLUSION(S)
Intranasal GnRHa is effective in achieving luteal-phase support in high-responder patients triggered with GnRHa and avoiding OHSS.
Topics: Administration, Intranasal; Adult; Drug Administration Schedule; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone, Human; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Infertility; Menotropins; Nafarelin; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Recombinant Proteins; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 27114332
DOI: 10.1016/j.fertnstert.2016.04.004 -
Fertility and Sterility Aug 2016To investigate flexibility in starting controlled ovarian stimulation at any phase of the menstrual cycle in infertile women undergoing treatment with assisted... (Comparative Study)
Comparative Study
Flexibility in starting ovarian stimulation at different phases of the menstrual cycle for treatment of infertile women with the use of in vitro fertilization or intracytoplasmic sperm injection.
OBJECTIVE
To investigate flexibility in starting controlled ovarian stimulation at any phase of the menstrual cycle in infertile women undergoing treatment with assisted reproduction.
DESIGN
Retrospective cohort study.
SETTING
Academic tertiary-care medical center.
PATIENT(S)
At total of 150 infertile patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Ninety of the women also underwent frozen embryo transfer (FET) procedures.
INTERVENTION(S)
Depending on the phase of the menstrual cycle when ovarian stimulation was started, three groups of patients were identified, namely: conventional group (ovarian stimulation started in the early follicular phase), late follicular phase group, and luteal phase group. When dominant follicles were observed, final oocyte maturation was triggered with the use of GnRH agonist and hCG. In all three groups, viable embryos were cryopreserved for subsequent transfer.
PRIMARY OUTCOME
number of mature oocytes retrieved.
SECONDARY OUTCOMES
fertilization rate, viable embryo rate per oocyte retrieved, cancellation rate, and clinical pregnancy outcomes from FET cycles.
RESULTS(S)
There were no differences in the mean number of mature oocytes retrieved in the conventional group, late follicular phase group, and luteal phase group (5.7 ± 3.6, 5.2 ± 3.7, and 5.2 ± 3.9, respectively). Similarly, no significant differences were observed in the viable embryo rate per oocyte retrieved (37.9%, 38.5%, and 43.6%), clinical pregnancy rates (41.5%, 45.5%, and 38.9%), and implantation rates (30.7%, 30.2%, and 27.1%) in the three groups.
CONCLUSION(S)
All three ovarian stimulation protocols were observed to be equally effective. These results demonstrate that ovarian stimulation can be commenced on any day of the menstrual cycle.
CLINICAL TRIAL REGISTRATION NUMBER
ChiCTR-OPN-15007332.
Topics: Adult; China; Chorionic Gonadotropin; Cryopreservation; Drug Administration Schedule; Embryo Implantation; Embryo Transfer; Female; Fertility; Fertility Agents, Female; Fertilization in Vitro; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Medroxyprogesterone Acetate; Menotropins; Oocyte Retrieval; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Tertiary Care Centers; Treatment Outcome; Triptorelin Pamoate
PubMed: 27114329
DOI: 10.1016/j.fertnstert.2016.04.006 -
Medicine Mar 2016Ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Controlled Ovarian Stimulation Using Medroxyprogesterone Acetate and hMG in Patients With Polycystic Ovary Syndrome Treated for IVF: A Double-Blind Randomized Crossover Clinical Trial.
Ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation is a current challenge for patients with polycystic ovarian syndrome (PCOS). Our previous studies indicated that progestin can prevent premature luteinizing hormone (LH) surge or moderate/severe OHSS in the general subfertile population, both in the follicular-phase and luteal-phase ovarian stimulation but it is unclear if this is true for patients with PCOS. The aim of the article was to analyze cycle characteristics and endocrinological profiles using human menopausal gonadotropin (hMG) in combination with medroxyprogesterone acetate (MPA) for PCOS patients who are undergoing IVF/intracytoplasmic sperm injection (ICSI) treatments and investigate the subsequently pregnancy outcomes of frozen embryo transfer (FET). In the randomized prospective controlled study, 120 PCOS patients undergoing IVF/ICSI were recruited and randomly classified into 2 groups according to the ovarian stimulation protocols: hMG and MPA (group A, n = 60) or short protocol (group B, n = 60). In the study group, hMG (150-225IU) and MPA (10 mg/d) were administered simultaneously beginning on cycle day 3. Ovulation was cotriggered by a gonadotropinreleasing hormone (GnRH) agonist (0.1 mg) and hCG (1000IU) when dominant follicles matured. A short protocol was used as a control. The primary end-point was the ongoing pregnancy rate per transfer and incidence of OHSS. Doses of hMG administrated in group A are significantly higher than those in the controls. LH suppression persisted during ovarian stimulation and no incidence of premature LH surge was seen in both groups. The fertilization rate and the ongoing pregnant rate in the study group were higher than that in the control. The number of oocytes retrieved, mature oocytes, clinical pregnancy rates per transfer, implantation rates, and cumulative pregnancy rates per patient were comparable between the 2 groups. The incidence of OHSS was low between the 2 groups, with no significant difference. The study showed that MPA has the advantages of an oral administration route, easy access, more control over LH levels. A possible reduction in the incidence of moderate or severe OHSS with the MPA protocol should be viewed with caution as the data is small. Large randomized trials with adequate sample size remain necessary.
Topics: Administration, Oral; Adult; Cross-Over Studies; Double-Blind Method; Embryo Transfer; Female; Fertilization; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Medroxyprogesterone Acetate; Menotropins; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; Prospective Studies; Sperm Injections, Intracytoplasmic
PubMed: 26945402
DOI: 10.1097/MD.0000000000002939 -
Medicine Mar 2016Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and... (Observational Study)
Observational Study
Gonadotropin induces masculinization and spermatogenesis in men with congenital hypogonadotropic hypogonadism (CHH). However, large cohort studies for the efficacy and reliable predictors of this therapy need to be conducted. The aim of this study was to investigate the efficacy of gonadotropin treatment in a large cohort of male CHH patients and analyze putative predictors for successful spermatogenesis. This retrospective study included 223 CHH azoospermic patients without puberty development treated between 2005 and 2014. All patients received combined human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) and were followed up for >6 months (5109 person-months). Serum total testosterone level, testicular size, spermatogenesis, and pregnancy outcome were recorded at each visit. After gonadotropin therapy, testicular size was enlarged from 2.1 ± 1.6 to 8.1 ± 4.6 mL (P < 0.001) and serum total testosterone was elevated from 0.9 ± 0.5 to 15.1 ± 8.2 nmol/L (P < 0.001). Spermatogenesis (>0/mL) occurred at a median period of 15 months (95% confidence interval 13.5-16.5). Larger basal testicular volume (P = 0.012) and noncryptorchidism history (P = 0.028) are independent predictors for earlier sperm appearance. Sixty four percent (143/223) of patients succeeded in producing sperms and the average time for initial sperm detection was 14 ± 8 months. However, their sperm concentrations (11.7 [2.1, 24.4] million/mL) and sperm progressive motility (A + B 36.9% ± 20.2%) are significantly lower than World Health Organization standards. Of the 34 patients who desired for fathering children, 19 patients impregnanted their partners during the treatment. Gonadotropin therapy induces spermatogenesis in male CHH patients. A larger basal testicular size and noncryptorchidism history are favorable indicators for earlier spermatogenesis.
Topics: Chorionic Gonadotropin; Drug Therapy, Combination; Humans; Hypogonadism; Male; Menotropins; Retrospective Studies; Spermatogenesis; Treatment Outcome; Young Adult
PubMed: 26945370
DOI: 10.1097/MD.0000000000002867 -
Taiwanese Journal of Obstetrics &... Feb 2016Poor ovarian response to ovarian hyperstimulation is one of the biggest challenges in assisted reproduction technology. Although many stimulation protocols have been... (Comparative Study)
Comparative Study
Luteal-phase ovarian stimulation is a feasible method for poor ovarian responders undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer treatment compared to a GnRH antagonist protocol: A retrospective study.
OBJECTIVE
Poor ovarian response to ovarian hyperstimulation is one of the biggest challenges in assisted reproduction technology. Although many stimulation protocols have been established to improve clinical outcomes in poor ovarian responders (PORs), which protocol is the most effective remains controversial. Luteal-phase ovarian stimulation (LPOS) has been used in normal ovarian responders with satisfactory outcomes. However, the efficacy of LPOS in PORs is unclear. This study aimed to compare the efficacy of LPOS and GnRH antagonist (GnRH-ant) in PORs.
MATERIALS AND METHODS
The clinical parameters in PORs who received LPOS (50 cycles in 39 patients) or GnRH-ant (158 cycles in 123 patients) were compared.
RESULTS
Compared with those in the GnRH-ant group, the PORs in the LPOS group showed significantly fewer basal antral follicles (3.1 ± 2.2 vs. 4.1 ± 1.6, p < 0.001) and a higher in vitro fertilization rate. There were no significant differences in the numbers of retrieved oocytes and D3 transferable embryos between the two groups. However, the pregnancy rate in the LPOS group (46.4%) was significantly higher than that in the GnRH-ant group (25.8% overall; 22.9% from fresh embryos and 29.6% from frozen embryos). Moreover, 23 PORs in the LPOS group underwent oocyte retrieval twice in one cycle, and the numbers of retrieved oocytes and transferable embryos from the luteal phase were significantly higher than those from the follicular phase in the same menstrual cycle.
CONCLUSIONS
Compared with the GnRH-ant protocol, the LPOS protocol may be a better regime for PORs that can increase the numbers of retrieved oocytes and transferable embryos as well as the pregnancy rate.
Topics: Adult; Clomiphene; Embryo Transfer; Feasibility Studies; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Letrozole; Luteal Phase; Menotropins; Nitriles; Oocyte Retrieval; Ovarian Follicle; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Sperm Injections, Intracytoplasmic; Triazoles
PubMed: 26927248
DOI: 10.1016/j.tjog.2015.07.001 -
The Kaohsiung Journal of Medical... Jan 2016Infertility due to low testosterone levels has increased in recent years. This has impacted the social well-being of the patients. This study was undertaken to...
Infertility due to low testosterone levels has increased in recent years. This has impacted the social well-being of the patients. This study was undertaken to investigate the potential of gonadotropins in facilitating differentiation of human bone marrow mesenchymal stem cells (BMSCs) into Leydig cells in vitro. BMSCs were isolated, cultured, and their biological characteristics were observed. BMSCs were induced with gonadotropins in vitro and their ability to differentiate into Leydig cells was studied. The level of expression of 3-beta hydroxysteroid dehydrogenase (3β-HSD) and secretion of testosterone were determined using flow cytometry and enzyme-linked immunosorbent assay, respectively, and the results were compared between the experimental and control groups. The cultured BMSCs showed a typical morphology of the fibroblast-like colony. The growth curve of cells formed an S-shape. After inducing the cells for 8-13 days, the cells in the experimental group increased in size and showed typical characteristics of Leydig cells, and the growth occurred in spindle or stellate shapes. Cells from the experimental group highly expressed 3β-HSD, and there was a gradual increase in the number of Leydig cells. The control group did not express 3β-HSD. The level of testosterone in the experimental group was higher than the control group (p < 0.05). Additionally, the cells in the experimental group secreted higher levels of testosterone with increased culture time. The expression of Leydig cell-specific markers in the experimental group was significantly higher (p < 0.05). With these findings, BMSCs can be considered a new approach for the treatment of patients with low androgen levels.
Topics: 3-Hydroxysteroid Dehydrogenases; Adult; Bone Marrow Cells; Cell Differentiation; Cell Proliferation; Cell Shape; Cells, Cultured; Chorionic Gonadotropin; Female; Humans; Leydig Cells; Luteinizing Hormone; Male; Menotropins; Mesenchymal Stem Cells; Testosterone; Young Adult
PubMed: 26853168
DOI: 10.1016/j.kjms.2015.10.008 -
Drug Design, Development and Therapy 2015Gonadotropin has been used to stimulate ovulation in clomiphene-resistant infertile women with polycystic ovary syndrome (PCOS), but it is associated with overstimulated... (Comparative Study)
Comparative Study
BACKGROUND
Gonadotropin has been used to stimulate ovulation in clomiphene-resistant infertile women with polycystic ovary syndrome (PCOS), but it is associated with overstimulated cycles with the development of many follicles. The aim of the study was to evaluate the effectiveness and efficacy of letrozole and clomiphene citrate (CC) combined with human menopausal gonadotropin (HMG) in CC-resistant infertile women with PCOS.
METHODS
Ninety-four women received the letrozole + HMG, 90 women received CC + HMG, and 71 women received HMG only. All women received one treatment regimen in one treatment cycle. All patients were given HMG 75 IU on alternate days daily starting on day 3 or day 7 until the day of administration of human chorionic gonadotropin.
RESULTS
The rate of monofollicular development was 80.2% in the letrozole + HMG group, 65.3% in the CC + HMG group, and 54.7% in the HMG-only group (P<0.05 for letrozole + HMG vs the other two groups). The number of developing follicles (≥14 mm follicles) and the cycle cancellation rate due to ovarian hyperresponse were the lowest in the letrozole + HMG group, but the difference was not significant. The ovulation and pregnancy rate were similar among the three protocols. The HMG dose needed and the mean duration of treatment were significantly lower in the letrozole + HMG and CC + HMG groups compared with the HMG-only group.
CONCLUSION
Letrozole in combination with HMG is an effective protocol for reducing the risks of hyperstimulation for ovarian induction in CC-resistant women with PCOS. This combination may be more appropriate in patients who are particularly sensitive to gonadotropin.
Topics: Adult; Clomiphene; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fertility Agents, Female; Humans; Infertility, Female; Letrozole; Menotropins; Nitriles; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Prospective Studies; Treatment Outcome; Triazoles; Young Adult
PubMed: 26648691
DOI: 10.2147/DDDT.S83259 -
Reproductive Biology and Endocrinology... Nov 2015Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate.
OBJECTIVE
Increased progesterone level during follicular phase seemed to be associated with decreased pregnancy rate.
STUDY DESIGN AND METHODS
A prospective cohort study, 1.1.2012 - 31.8.13. The Progesterone (P) and Progesterone/Estrogen (P/E2) level on ovulation induction day were compared between the protocols and the different gonadotropins used. Roc analysis was calculated to determine the cutoff of P/E2 to predict delivery rates. P/E2 ratio was calculated as PX1000/e2 level.
MAIN RESULTS
One hundred thirty-nine patients were enrolled to the study. No difference in the P level at hCG stimulation day between different protocols, however, E2 and P/E2 ratio were significantly lower in the long protocol compare with antagonist protocol 1757.7 ± 923.2 vs. 1342.9 ± 1223; P = 0.003 and 0.48 ± 0.31 vs. 0.83 ± 0.87; P = 0.038). The endometrium was significantly thicker in the long group compare with short and antagonist. Significantly more top-quality embryos (TOP) were achieved in the antagonist group. Comparable results between the types of gonadotropins used in regards with cycle characteristics and pregnancy and delivery rates. The P/E2 ratio which can predict live birth rate was found to be 0.45, AUC = 0.632, p = 0.02 and 95 % CI 0.525-0.738 and a significantly higher pregnancy and delivery rates at a P/E2 bellow 0.45.
CONCLUSION
Endometrial receptivity is determined by the complex interactions of E2 and P.
Topics: Adult; Drug Therapy, Combination; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Follicular Phase; Humans; Menotropins; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Prospective Studies; Treatment Outcome
PubMed: 26542686
DOI: 10.1186/s12958-015-0116-y -
Fertility and Sterility Dec 2015To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To compare the outcomes of controlled ovarian stimulation/in vitro fertilization cycles using 450 IU and 600 IU gonadotropin per day in women at risk of poor ovarian response.
DESIGN
Prospective randomized controlled nonblinded study.
SETTING
University-affiliated private IVF center.
PATIENT(S)
Women considered to be at risk of poor ovarian response: aged <41 years with basal FSH >10 IU/L, antimüllerian hormone <1 ng/mL, antral follicle count ≤ 8, or a previous IVF cycle with ≥ 300 IU/d gonadotropin that resulted in a cancellation, <8 follicles, or <5 oocytes.
INTERVENTION(S)
A total of 356 patients underwent a microdose GnRH agonist flare-up IVF/intracytoplasmic sperm injection protocol with a fixed daily dose of either 450 IU FSH (n = 176) or 600 IU FSH (n = 180) equally divided between Menopur and Bravelle.
MAIN OUTCOME MEASURE(S)
Number of mature oocytes retrieved.
RESULT(S)
The two groups were similar in terms of age, ovarian reserve, cause of infertility, duration of stimulation, and cycle cancellation rate. There were no significant differences in the number of metaphase II oocytes retrieved (4 [range 0-6] vs. 4 [range 2-7]), fertilization rate (62.4% vs. 57.0%), biochemical pregnancy rate (20.5% vs. 22.9%), clinical pregnancy rate (16.4% vs. 18.3%), and implantation rate (29.8% vs. 30.4%) between the 450 IU and 600 IU groups, respectively.
CONCLUSION(S)
Gonadotropin of 600 IU/d does not improve outcome of IVF cycles compared with 450 IU/d in women at risk of poor ovarian response.
CLINICAL TRIAL REGISTRATION NUMBER
NCT00971152.
Topics: Adult; Embryo Implantation; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Follicle Stimulating Hormone; Humans; Infertility; Menotropins; Oocyte Retrieval; Ovary; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Prospective Studies; Quebec; Sperm Injections, Intracytoplasmic; Treatment Outcome; Urofollitropin
PubMed: 26361207
DOI: 10.1016/j.fertnstert.2015.08.014 -
Reproductive Biology and Endocrinology... Jul 2015The association of recombinant FSH (rFSH) plus recombinant LH (rLH) is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its efficacy has, to... (Comparative Study)
Comparative Study
Controlled Ovarian Stimulation with recombinant-FSH plus recombinant-LH vs. human Menopausal Gonadotropin based on the number of retrieved oocytes: results from a routine clinical practice in a real-life population.
BACKGROUND
The association of recombinant FSH (rFSH) plus recombinant LH (rLH) is currently used for Controlled Ovarian Stimulation (COS) in human IVF, but its efficacy has, to date, not yet been compared to that of human Menopausal Gonadotropin (hMG), the FSH + LH activity-containing urinary drug.
METHODS
Eight hundred forty-eight (848) IVF patients classified as expected "poor" or "normal" responders according to antral follicle count (AFC) and basal (day 3) FSH were treated with rFSH + rLH (2:1 ratio, n = 398, Group A) or hMG (n = 450, Group B). Data were collected under real-life practice circumstances and the pregnancy rate with fresh embryos was calculated by stratifying patients according to the number of retrieved oocytes (1-2, 3-4, 5-6, 7-8, >8).
RESULTS
Overall, the pregnancy rate in both groups progressively improved according to the number of oocytes retrieved. When comparing patients within the same subgroup of oocyte yield, Group A and B showed a comparable outcome up to the reported highest yield (>8). When more than 8 oocytes were available, Group A had a significantly better pregnancy rate outcome. Patients' characteristics did not significantly differ between the two groups and the better outcome in the best responding patients in Group A was confirmed by a multivariable logistic regression analysis, that showed that both the use of rFSH + rLH and the total number of retrieved oocytes increased the probability of pregnancy with odd ratio (OR) of 1.628 and 1.083, respectively.
CONCLUSIONS
When comparing patients with the same number of retrieved oocytes under real-life circumstances, the association of rFSH + rLH results in a significantly higher pregnancy rate than hMG when more than 8 oocytes are retrieved. The reason(s) for this are unknown, but a more favorable effect on oocyte quality and/or endometrial receptivity could be involved.
Topics: Adult; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Menotropins; Oocyte Retrieval; Oocytes; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Recombinant Proteins; Treatment Outcome
PubMed: 26209525
DOI: 10.1186/s12958-015-0080-6