lhrh--ala(6)-gly(10)-ethylamide- and Infertility--Female

The role of gonadotropins in the genesis of malignant diseases, in particular gynecologic cancers, is still controversial. The production of ovarian steroids, as a consequence of FSH and LH actions, may constitute a bias to draw reliable conclusions. Over the past decades, the use of exogenous gonadotropins has markedly increased in cancer patients, candidates for fertility preservation, and in survivors facing infertility as a consequence of gonadotoxic treatments. In gynecologic cancers, high serum estradiol levels may be problematic and can therefore be overcome by specific protocols of ovarian stimulation. However, exogenous gonadotropin administration in cancer patients should systematically be included in a multidisciplinary approach. The present article discusses the possible role of gonadotropins as tumorigenic factors and the use of exogenous gonadotropins in females suffering from cancer.

Topics: Adult; Animals; Disease Models, Animal; Female; Fertility Preservation; Follicle Stimulating Hormone; Genital Neoplasms, Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Luteinizing Hormone; Neoplasms; Ovulation Induction; Receptors, FSH

Abnormal luteal function is a common issue in assisted reproduction techniques associated with ovarian stimulation probably due to low levels of LH in the middle and in the late luteal phase. This defect seems to be associated with supraphysiological steroid levels at the end of follicular phase. The luteal phase insufficiency has not got a diagnostic test which has proven reliable in a clinical setting. Luteal phase after ovarian stimulation becomes shorter and insufficient, resulting in lower pregnancy rates. Luteal phase support with progesterone or hCG improves pregnancy outcomes and no differences are found among different routes of administration. However, hCG increases the risk of ovarian hyperstimulation syndrome. In relation to the length of luteal support, the day of starting it remains controversial and it does not seem necessary to continue once a pregnancy has been established. After GnRHa triggering ovulation, intensive luteal support or hCG bolus can overcome the defect in luteal phase, but more studies are needed to show the LH utility as support.

Topics: Chorionic Gonadotropin; Estradiol; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Ovarian Hyperstimulation Syndrome; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone

Previous studies found a poor clinical outcome when a GnRH agonist (GnRHa) was used to trigger ovulation in GnRH antagonist IVF/ICSI cycles. This study aimed to determine the clinical and endocrine effects as well the optimal timing of HCG supplementation. Forty-five normogonadotrophic IVF/ICSI patients following a flexible antagonist protocol were prospectively randomized (sealed envelopes) to triggering of ovulation with a single bolus of either 10,000 IU of HCG (group 1, n = 15) or 0.5 mg buserelin s.c. In addition, the GnRHa triggered group was randomized into two groups: group 2 (n = 17) was supplemented with HCG 1500 IU, 12 h after ovulation induction and group 3 (n = 13) was supplemented with HCG 1500 IU 35 h after ovulation induction. Group 1 and group 3 had significantly higher luteal phase concentrations of progesterone (P < 0.001) as compared with group 2. Moreover, the clinical pregnancy rate of groups 1 and 3 was similar and significantly higher (P < 0.02) than that of group 2. A larger study, however, is required to substantiate these differences. No differences were seen regarding mid-luteal inhibin A concentrations between the three groups. Triggering of ovulation with GnRHa supplemented with 1500 IU HCG 35 h later (group 3) seems to secure a normal luteal phase and a normal clinical pregnancy outcome.

Topics: Chorionic Gonadotropin; Corpus Luteum; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Inhibins; Ovulation; Ovulation Induction; Pilot Projects; Pregnancy; Pregnancy Rate; Progesterone; Sperm Injections, Intracytoplasmic

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome (OHSS), characterized by more than 30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL, which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist (GnRHa) trigger and freeze-all policy that previously have been reported. All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards. The in vitro fertilization (IVF) outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS. Moreover, patients' symptoms, reproductive hormone levels and ultrasound findings were improved significantly. This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS, especially for the patients characterized by ≤30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL. Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

Topics: Adult; Estradiol; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Oocyte Retrieval; Ovarian Follicle; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate

Adenomyosis is a common gynaecological disorder that is associated with infertility and miscarriage. We report a case of adenomyosis presented with urinary retention and infertility. The patient successfully conceived spontaneously following GnRHa followed by progestogen therapy. This treatment option might provide a synergistic effect in improving fertility and pregnancy outcome for women with adenomyosis. This modality has no potential surgical risk; it minimises the long-term side effects of GnRHa and also provides luteal support.

Topics: Adenomyosis; Adult; Drug Synergism; Dydrogesterone; Female; Fertilization; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Pregnancy; Progestins

Additional treatment with a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) before IVF-ET (ultralong GnRHa therapy) has been reported to improve the outcome of IVF-ET in endometriosis patients. However, the mechanism of ultralong GnRHa therapy is unclear. It is suggested that inflammatory cytokines and oxidative stress contribute to infertility in endometriosis patients. Therefore, in order to search a possible mechanism of ultralong GnRHa therapy, we investigated the effect of ultralong GnRHa therapy on intrafollicular concentrations of tumor necrosis factor alpha (TNFα), oxidative stress markers, and antioxidants in patients with endometriosis.. Twenty-three infertile women with Stage III or IV endometriosis were recruited for this study. Eleven patients received three courses of GnRHa (1.8 mg s.c. every 28 days), followed by a standard controlled ovarian hyperstimulation (COH) for IVF-ET (ultralong group). The other 12 patients received a standard COH with mid-luteal phase GnRHa down-regulation (control group). The numbers of matured follicles and retrieved oocytes, fertilization rates, implantation rates, clinical pregnancy rate, and intrafollicular concentrations of TNFα, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct (HEL) as oxidative stress markers, and melatonin and Cu,Zu-superoxide dismutase (Cu,Zn-SOD) as antioxidants were compared between the two groups.. The numbers of mature follicles and retrieved oocytes, and fertilization rates did not differ between the two groups. Implantation rates and pregnancy rates tended to be higher in the ultralong group (21.4% and 27.3%, respectively) compared with the control group (8.3% and 8.3%, respectively). TNFα concentrations in the follicular fluid were significantly lower in the ultralong group (5.8 ± 3.2 pg/ml) than those in the control group (10.6 ± 3.2 pg/ml). Follicular concentrations of 8-OHdG concentrations were significantly lower in the ultralong group (5.7 ± 1.6 ng/ml) than those in the control group (6.6 ± 1.5 ng/ml), while melatonin concentrations were significantly higher in the ultralong group (139 ± 46 pg/ml) compared with the control group (86 ± 27 pg/ml).. Ultralong GnRHa therapy reduces the detrimental effects of cytotoxic cytokines and oxidative stress in the ovary in patients with endometriosis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Deoxyguanosine; Endometriosis; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Melatonin; Ovulation Induction; Oxidative Stress; Pilot Projects; Pregnancy; Pregnancy Rate; Superoxide Dismutase; Treatment Outcome; Tumor Necrosis Factor-alpha

To compare live birth rates after dual trigger of oocyte maturation with GnRH agonist (GnRHa) and low-dose hCG versus GnRHa alone in high responders with peak E(2) <4,000 pg/mL at risk of ovarian hyperstimulation syndrome (OHSS).. Retrospective cohort study.. University-based tertiary-care fertility center.. Patients <40 years old with peak E(2) <4,000 pg/mL at risk of OHSS who underwent IVF/intracytoplasmic sperm injection with GnRH antagonist protocol and triggered with GnRHa alone or GnRHa plus 1,000 IU hCG (dual trigger) for oocyte maturation.. GnRHa alone versus dual trigger.. Live birth, implantation, and clinical pregnancy rates and OHSS.. The dual-trigger group had a significantly higher live birth rate (52.9% vs. 30.9%), implantation rate (41.9% vs. 22.1%), and clinical pregnancy rate (58.8% vs. 36.8%) compared with the GnRHa trigger group. One case of mild OHSS occurred in the dual-trigger group, and there were no cases of OHSS in the GnRHa trigger group.. Dual trigger of oocyte maturation with GnRHa and low-dose hCG in high responders with peak E(2) <4,000 pg/mL improves the probability of conception and live birth without increasing the risk of significant OHSS.

Topics: Abortion, Spontaneous; Adult; Chorionic Gonadotropin; Databases, Factual; Dose-Response Relationship, Drug; Drug Therapy, Combination; Embryo Implantation; Female; Gonadotropin-Releasing Hormone; Humans; Infertility, Female; Luteal Phase; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Reproductive Control Agents; Retrospective Studies; Risk Factors

To evaluate the levels of bone morphogenetic protein-15 (BMP-15) in human follicular fluid (FF) and its association with response to ovarian stimulation.. Western blotting was performed to determine the levels of BMP-15 in FF obtained from follicle aspirates in 70 patients undergoing IVF treatment. According to the response to ovarian stimulation the patients were divided into poor responder group and normal responder group.. BMP-15 levels in FF of poor responders were significantly higher than those in normal responders (1.01 +/- 0.34 vs 0.77 +/- 0.24, P<0.01).. Increased levels of BMP-15 in FF may be associated with poor response to ovarian stimulation.

Topics: Adult; Blotting, Western; Bone Morphogenetic Protein 15; Female; Follicle Stimulating Hormone; Follicular Fluid; Gonadotropin-Releasing Hormone; Growth Differentiation Factor 9; Humans; Infertility, Female; Intercellular Signaling Peptides and Proteins; Ovary; Ovulation Induction

To analyze the results and complications of ovulation induction therapy (OIT) in women with systemic lupus erythematosus (SLE) and/or the antiphospholipid syndrome (APS).. A retrospective study of 21 women followed in a single tertiary-referral French center who underwent 114 OIT cycles with or without in vitro fertilization and embryo transfer (IVFET).. Before OIT, SLE was present in 6 women, APS in 3, SLE-related APS in 3, and discoid lupus in 1. Eight women had no identified disease and underwent 36 cycles of OIT. Diagnosis (SLE, n = 3; primary APS, n = 5) was made after OIT complication: spontaneous abortion (n = 5), SLE flare (n = 2), and thrombophlebitis (n = 1). Five women with known disease intentionally concealed their history from their gynecologists and underwent 34 cycles. Forty-four cycles were planned in 11 women, in 3 of them after complications of prior OIT performed without particular therapy and monitoring. Eighteen pregnancies occurred, which ended in 9 live births, 4 fetal deaths, and 5 embryonic losses. The pregnancy rate was higher with gonadotropin and/or gonadotropin-releasing hormone analog (GnRHa) (25% of cycles) than with clomiphene (4% of cycles, P <.0001). When the gynecologists did not know the underlying disease, three-quarters of pregnancies induced by OIT with IVFET ended in embryonic losses or fetal deaths. In contrast, 6 of 7 pregnancies induced by planned OIT with IVFET ended in live births (P <.0001). Phlebothromboses were observed only with gonadotropin treatment. The SLE flare rate was higher with gonadotropin and/or GnRHa (27% of cycle) than with clomiphene (6%, NS). It also was higher (30%) when the gynecologists did not know the underlying disease than in the planned procedures (10%, NS).. The OIT may precipitate SLE or APS. A careful review of the patient's history and appropriate laboratory tests should be undertaken before OIT. Clomiphene complications are rare. When gonadotropins are prescribed, preventive anti-inflammatory therapy should be considered in women with SLE, in addition to heparin and/or anti-aggregant therapy in patients with asymptomatic anti-phospholipid antibodies or prior thrombotic events.

Topics: Adult; Antiphospholipid Syndrome; Embryo Transfer; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Lupus Erythematosus, Systemic; Ovulation Induction; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Rate; Retrospective Studies