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1.
The renewed interest in luteinizing hormone (LH), together with limited and decreasing health resources, make essential the comparison of high-cost, recombinant follicle-stimulating hormone (rFSH) preparations (devoid of LH) and human menopausal gonadotropin (hMG) in terms of clinical efficacy. All published, randomized controlled trials (RCTs) comparing rFSH versus hMG under different protocols of stimulation were examined. Eight true RCTs were included in this meta-analysis, recruiting 2031 participants. Data for ongoing pregnancy/live birth rate, clinical pregnancy rate, miscarriage rate, multiple pregnancy rate and ovarian hyperstimulation syndrome (OHSS) were extracted, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with the use of a fixed-effects model. Data for the meta-analysis were combined using RevMan software (using the Mantel–Haenszel method). Pooling the results of these RCTs showed no significant difference between rFSH and hMG regarding the different outcomes: ongoing pregnancy/live birth rate, OR 1.18 (95% CI 0.93–1.50); clinical pregnancy rate, OR 1.2 (95% CI 0.99–1.47), miscarriage rate, OR 1.2 (95% CI 0.70–2.16); multiple pregnancy rate, OR 1.35 (95% CI 0.96–1.90); incidence of moderate/severe OHSS, OR 1.79 (95% CI 0.74–4.33). However, there was significant reduction in the amount of gonadotropins in favor of hMG over rFSH. There was no significant heterogeneity of treatment effect across the trials. In conclusion, there is no clinically significant difference between hMG and rFSH in in vitro fertilization/intracytoplasmic sperm injection cycles. Decision-makers should establish their choice of one drug over the other based on the most up-to-date evidence available.  相似文献   

2.
Objective: To discuss the clinical therapeutic window for LH during the follicular phase.

Design: Review of selected papers that were retrieved through a Medline search and a review of clinical trials, the results of which are in the process of publication.

Patient(s): Women undergoing infertility treatment.

Intervention(s): Recombinant human LH (r-hLH) was administered SC as a supplement to FSH during controlled ovarian hyperstimulation.

Main Outcome Measure(s): Follicular development, E2 production, and endometrial thickness.

Result(s): Optimal follicular maturation is the result of both FSH and LH stimulation. In patients with hypogonadotropic hypogonadism, 75 IU of r-hLH and 150 IU of FSH per day resulted in more follicles and provided sufficient E2 for optimal endometrial proliferation. Additional r-hLH (>250 IU/day), in patients with either hypogonadotropic hypogonadism or polycystic ovary disease, may precipitate a series of deleterious physiological actions leading to atresia of developing follicles. Adding r-hLH to FSH in women treated with GnRH agonist showed no benefits in terms of number of mature oocytes, fertilization, and cleavage. However, those who experience profound pituitary desensitization may benefit from adding LH to the stimulation protocol. No obvious clinical criteria have been established to define this group of patients.

Conclusion(s): A “threshold” and “ceiling” level for LH (therapeutic window) is proposed, below which E2 production is not adequate and above which LH may be detrimental to follicular development.  相似文献   


3.
There is a distinct pattern of response to gonadotropin stimulation in some patients marked by high peak estradiol (E2) levels, multifollicular ovarians response, and elevated basal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios. We reviewed the stimulation profiles of five such high-responder patients who failed to conceive during in vitro fertilization with ovarian stimulation using pure FSH. All patients had baseline LH/FSH >1.5 and peak E2>800 pg/ml. One cycle was canceled prior to hCG administration because of marked ovarian response (E2>2500 pg/ml, multiple small follicles). In a subsequent cycle, all patients were pretreated with the gonadotropin releasing-hormone agonist (GnRHa) leuprolide acetete for 10–14 days prior to initiation of FSH for ovarian stimulation. Leuprolide was continued until the day of hCG administration. During cycles using GnRHa, there was a statistically significant decrease (P <0.05) in serum FSH on day 3 (<5 vs 8.3 mIU/ml), serum E2 on day 3 (14.6 vs 34.6 pg/ml), and peak serum E2 (1197.6 vs 1923.0 pg/ml). Patients during cycles with GnRHa had a greater number of preovulatory (8.6 vs 3.0) and total (12.4 vs 6.0) oocytes retrieved (P<0.05). The fertilization rate of preovulatory oocytes was also higher during cycles using GnRHa (83 vs 64%). Two pregnancies occurred in the cycles pretreated with GnRHa. These preliminary data indicate that in high-responder patients, a combination of GnRHa and pure FSH results in lower E2 levels during the stimulation cycle and a greater number of total and mature oocytes retrieved and fertilized.  相似文献   

4.
Purpose: Impaired outcome of in vitro fertilization treatment has been related to abnormal luteining hormone (LH) secretion and to the occurrence of a premature LH surge. The purpose of this study was to compare LH serum concentrations, measured by bioassay (LH-b) and immunoassay (LH-i), during early and late follicular phases in normal-ovulatory women who were stimulated with clomiphene, human menopausal gonadotropin (HMG), and human chorionic gonadotropin (hCG), while undergoing in vitro fertilization (IVF) treatment for infertility, due mainly to tubal damage. Results: Of 22 patients, 15 had an LH surge (surge group) before receiving hCG and 7 did not (nonsurge group). LH-b and LH-i concentrations were higher in the late follicular phase than before clomiphene treatment, but the LH-b/LH-i (B/I) ratios remained unchanged and there were no significant differences between the LH surge and the nonsurge groups. In the surge group, the B/I ratio appeared to fall during the LH surge [presurge values, 5.4 ± 0.5 (SD) and 5.2 ± 0.5; surge values, 4.9 ± 0.6 and later 4.0 ± 0.6], but the differences were not significant, and in some individuals, the B/I ratio later rose as the LH surge progressed. Conclusions: Our findings suggest that interference with IVF outcome by a spontaneous LH surge is due to quantitative and/or exposure time effects on the oocyte, rather than to any qualitative variation in bioactivity of LH.  相似文献   

5.
Objective.?This study was performed to evaluate the association between adding luteinizing hormone (LH) activity and the incidence of tripronuclear (3PN) zygotes occurrence.

Methods.?The incidence of 3PN and cycle outcomes was compared between recombinant follicle stimulating hormone (rFSH)-only and rFSH with exogenous LH activity groups. These comparisons were performed in gonadotropin releasing hormone (GnRHa, n?=?196) and gonadotropin releasing hormone antagonist (GnRHant, n?=?182) subgroups, and in in?vitro fertilisation (IVF) (n?=?243) and intracytoplasmic sperm injection (ICSI) (n?=?135) cycles, respectively.

Results.?The percentage of 3PN was significantly lower in LH activity-added group compared to rFSH-only group (3.6% vs. 5.6%, p?=?0.029). Both in GnRHa and GnRHant subgroups, this incidence tended to be lower in LH-supplemented group, although these differences did not reach statistical significance. In IVF cycles, LH activity-added group showed a lower 3PN rate versus rFSH-only group (4.0% vs. 6.7%, p?=?0.018). No difference of 3PN rate was found in ICSI cycles.

Conclusions.?Supplementation of exogenous LH activity to ovarian stimulation may be associated with lower prevalence of 3PN zygotes in IVF cycles, but not in ICSI cycles.  相似文献   

6.
Background.?Poor ovarian response to standard in vitro fertilization–embryo transfer (IVF-ET) protocols or different regimens of treatment, as consequence of a diminished ovarian reserve, correlates strictly with patient age, elevated follicle-stimulating hormone (FSH) and reduced antral follicle count. The aim of the present pilot study was to evaluate the outcome of patients with poor prognostic features undergoing IVF-ET with natural cycles as a first approach and not as a consequence of a previous failure treatment.

Materials and methods.?Eighteen aged patients (mean ± standard deviation 40.2 ± 0.7 years, range 37–43 years) with elevated serum FSH and reduced antral follicle count underwent intracytoplasmic sperm injection (ICSI) after spontaneous ovulation.

Results.?A total of 26 natural cycles with ICSI were analyzed. Pregnancy was observed in three patients, of which two were ongoing as assessed by fetal heart beat at ultrasound scan performed 4–5 weeks after ET.

Conclusion.?The overall pregnancy rates achieved (11.5% per cycle, 20.0% per ET) are comparable with those of conventional IVF-ET in aged patients, and not impaired by a single embryo transferred. Better embryo quality, as a consequence of natural selection of oocytes, better endometrium receptivity and monthly repeatability of the procedure, can balance the relatively low chance to perform ET.  相似文献   

7.
Follicle-stimulating hormone (FSH) was used in high doses (6 ampoules/day:6FSH) for ovarian hyperstimulation for in vitro fertilization in women with a previous voor response to stimulation with the equivalent of 4FSH. Luteinizing hormone levels did not differ between stimulations, but both FSH and estradiol levels were higher in the 6FSH compared to the 4FSH cycle. There were fewer cancellations in the 6FSH cycle, but similar numbers of preovulatory oocytes were retrieved, fertilized, and transferred. The pregnancy rates per attempt and retrieval were higher in the 6FSH cycle. We conclude that raising and maintaining FSH levels during stimulation in low responders reduced cancellations and may improve in vitro fertilization outcome.Presented in part at the 44th Annual Meeting of the American Fertility Society, Atlanta, Georgia, 1989, Abstract No. 52.  相似文献   

8.
Purpose: The study was conducted to evaluate levels of anticomplement in seminal plasma and levels of complement in follicular fluid, in correlation with fertilization and pregnancy rate after in vitro fertilization and intracytoplasmic sperm injection programs. Materials and Methods: Anticomplement levels were determined in 70 couples undergoing in vitro fertilization therapy. In 15 of these couples, complement levels were measured. Anticomplement and complement levels were also determined in an additional 21 couples (apart from the 70 couples) undergoing intracytoplasmic sperm injection treatment. Results: A correlation was found between fertilization rate and anticomplement levels in the seminal plasma (r=0.4,P<0.01) after standard in vitro fertilization. No correlation was found in the intracytoplasmic sperm injection group, or observed between complement levels and any parameter examined in both groups. Pregnancy occurred only in those couples with an anticomplement: complement ratio below 0.49. Conclusions: Determination of anticomplement and complement levels may contribute to the assessment of a successful outcome of in vitro fertilization/intracytoplasmic sperm injection.Presented in Part at the IXth World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, April 3–7, 1995, Vienna, Austria.  相似文献   

9.
10.
Objective: The aim of the presented study is to investigate the impact of progesterone change in the late follicular phase on the pregnancy rates of both agonist and antagonist protocols in normoresponders.

Study design: A total of 201 normoresponder patients, who underwent embryo transfer were consecutively selected. 118 patients were stimulated using a long luteal GnRH agonist protocol and 83 using a flexible antagonist protocol. The level of change in late follicular phase progesterone was calculated according to the progesterone levels on the hCG day and pre-hCG day (1 or 2 days prior to hCG day) measurement.

Results: Clinical pregnancy rates were comparable between long luteal and antagonist group (35.6 and 41%, respectively). The incidence of progesterone elevation on the hCG day was 11% in long luteal and 18% in antagonist group (p?=?0.16). In pregnant cycles, p levels both on the hCG day and pre-hCG day measurement were significantly higher in antagonist than agonist cycles (p?=?0.029, p?=?0.038, respectively). The change of p level was statistically significant in non-pregnant cycles both for the agonist (-0.17?±?0.07; 95% CI:??0.29 to??0.37) and antagonist groups (?0.18?±?0.07; 95%CI:??0.31 to??0.04).

Conclusions: Late follicular phase progesterone levels were stable during the cycles of pregnant patients irrespective of the protocols and were shown to be higher in pregnant patients in antagonist cycles when compared to agonist cycles.  相似文献   

11.
This study demonstrates that luteinizing hormone (LH) release may occur despite sustained elevations of estradiol E2 in women receiving human menopausal gonadotropin. Mean levels of E2 did not correlate with the LH surge, however, the follicle number and a rapid rise in E2 did. Therefore, it appears that the protective influence of inhibitory proteins secreted by multiple follicles can be overridden, allowing spontaneous LH release.  相似文献   

12.
Aim:  The mild ovarian stimulation protocol for in vitro fertilization (IVF) is carried out to minimize adverse side-effects as well as cost. While performing mild ovarian stimulation with a gonadotropin-releasing hormone (GnRH) antagonist, the pregnancy rate was examined in cases that exhibited a serum estradiol (E2) drop down.
Methods:  In this study, 174 patients who requested mild ovarian stimulation for IVF began clomiphene citrate on day 3 and recombinant follicle-stimulating hormone (FSH) on day 5 of their menstrual cycles. A GnRH antagonist was administered when the dominant follicle reached a diameter of 14 mm. Serum luteinizing hormone and estradiol were measured at the time of GnRH antagonist administration and at the time of human chorionic gonadotropin (hCG) injection. Pregnancy rates and implantation rates were compared between 24 cycles in which the E2 level fell at the time of hCG injection and 150 cycles in which it did not fall.
Results:  The pregnancy rate in the cases in which the E2 level fell (25% decrease) at the time of hCG injection was significantly lower than it was in the cases in which it did not fall (16.7 vs 41.0%). The implantation rate for the cases in which the E2 level fell was also lower than that of the control group (7.0 vs 31.0%). There was no significant difference in the number of good-quality embryos between the two groups.
Conclusion:  When performing the mild ovarian stimulation protocol, serum E2 should be followed. It is prudent to avoid embryo transfer in the same cycle in cases that exhibit E2 drop down. (Reprod Med Biol 2008; 7 : 85–89)  相似文献   

13.
PURPOSE: To report a successful pregnancy from cryopreserved sibling oocytes and intracytoplasmic sperm injection (ICSI) for an infertile couple with an unexpectedly low fertilization rate in the fresh in vitro fertilization (IVF) cycle. METHODS: The woman had bilateral tubal obstruction and polycystic ovarian syndrome. The man had normal semen parameters. The couple underwent a cycle of controlled ovarian hyperstimulation in that 20 oocytes were retrieved. Twelve oocytes were conventionally inseminated and eight were cryopreserved using a slow freezing method. However, only one oocyte was fertilized, and no pregnancy was achieved. In the next cycle, the frozen oocytes were thawed and ICSI was performed. RESULTS: After thawing, seven oocytes (88%) survived and one was damaged. Six were at the metaphase II stage and were injected. Five (83%) achieved normal fertilization, and all of them cleaved (100%). After replacement of the embryos, a singleton pregnancy developed. A healthy female baby was delivered at term. Karyotyping revealed 46, XX. CONCLUSIONS: In addition to well-known indications, cryopreservation of excess sibling oocytes for patients receiving IVF has a possible advantage of preventing unexpectedly low fertilization rate or fertilization failures.  相似文献   

14.
OBJECTIVE: To determine the relative efficacy of recombinant FSH (rFSH) and urinary FSH (uFSH) for ovarian stimulation in assisted reproductive techniques (ART). DESIGN: Systematic review and meta-analysis of randomized, controlled trials comparing rFSH and uFSH. SETTING: Infertility centers providing treatment with ART. PATIENT(S): Patients undergoing IVF with or without ICSI. INTERVENTION(S): Controlled ovarian stimulation using uFSH or rFSH (follitropin alpha or follitropin beta). MAIN OUTCOME MEASURE(S): Primary: rate of clinical pregnancy per cycle. Secondary: rates of spontaneous abortion, multiple pregnancy, and severe ovarian hyperstimulation syndrome (OHSS); total gonadotropin dose; serum E(2) level and number of follicles at hCG administration; number of oocytes retrieved. RESULT(S): Eighteen trials were included in the meta-analysis. Subgroup analyses demonstrated higher pregnancy rates with both follitropins compared with uFSH. However, statistical significance was reached only in the follitropin alpha versus uFSH comparison in IVF cycles, with an additional pregnancy for every 19 patients treated. Fewer units of rFSH than uFSH achieved the same E(2) level and oocyte yield. No differences were found between treatments in rates of spontaneous abortion, OHSS, and multiple gestation. CONCLUSION(S): rFSH produced higher pregnancy rates per cycle than uFSH when follitropin alpha was used in IVF, and the total gonadotropin dose required was lower.  相似文献   

15.
OBJECTIVE: To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG. DESIGN: Controlled, prospective, randomized comparison of fixed gonadotropin regimens. SETTING: Academic research institution. PATIENT(S): Fifty infertile patients who were candidates for IUI. INTERVENTION(S): Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen). MAIN OUTCOME MEASURES: Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications.Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ. CONCLUSION: The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha.  相似文献   

16.
Purpose: Our objective was to determine the effect of experience on the results with intracytoplasmic sperm injection. Methods: The quarterly outcome with both ICSI and traditionalin vitro fertilization (IVF) in 1994 was analyzed in 475 patients under age 40 undergoing 595 oocyte retrievals. The data represent 307 patients undergoing 379 retrievals for IVF and 165 patients undergoing 216 retrievals for ICSI. Results: Fertilization rates with ICSI improved significantly each quarter (52.96, 62.17, 70.17, and 74.87% in Q-I, Q-II, Q-III, and Q-IV, respectively), while the rate with IVF improved significantly between Q-I (69.9%) and Q-II (80.10%) and slightly but significantly between Q-II and Q-IV (82.88%). The implantation rate per embryo after ICSI improved significantly after Q-I (6.17%) compared to Q-II (10.70%) and Q-IV (12.14%). The pregnancy rate per transfer with ICSI increased steadily after Q-I (13.79, 21.88, 23.53, and 25.00% in Q-I through Q-IV), reaching statistical significance between Q-I and Q-III and between Q-I and Q-IV. Conclusions: Although acceptable results can be obtained with ICSI after a relatively short period of time, optimum results require substantial experience.  相似文献   

17.
18.
OBJECTIVE: To evaluate the efficacy of two doses of recombinant (r)LH, 75 IU (recommended) or 37.5 IU, for follicular stimulation and outcomes in a randomized cohort of IVF patients. DESIGN: Randomized, prospective analysis. SETTING: Private hospital incorporating an established IVF center. PATIENT(S): Women undergoing IVF who had a body mass index >18 or <35 and no abnormal karyotype, anovulation, oligomenorrhea, or any known endocrinopathy/illness. INTERVENTION(S): Pituitary desensitization was achieved with triptorelin (0.1 mg SC), and gonadotropin stimulation was performed with either rFSH alone (group A) or in combination with rLH in one of two doses: 37.5 IU (group B) or 75 IU (group C), daily. MAIN OUTCOME MEASURE(S): A range of endocrinologic, embryologic, clinical, and outcome parameters were evaluated. RESULT(S): With rLH supplementation there was a significant increase in the incidence of implantation (9% for rFSH only [group A] vs. 11% and 16% with 37.5 IU rLH and 75.0 IU rLH [groups B and C], respectively) and clinical pregnancy (19% vs. 23% and 31%) (P<.01 and P<.04, respectively), whereas there was no difference in the multiple pregnancy rates. There was a significant (P<.001) increase in the total units of rFSH used in proportion to the amount of rLH supplementation (2,645 U vs. 3,475 U and 3,681 U) and in the level of peripheral E(2) on the day of hCG administration (1,049 pg/mL vs. 1,640 pg/mL and 1,226 pg/mL) (P<.001). There was no significant between difference in mean age, numbers of oocytes recovered, basal and downregulation hormone levels, or the incidence of fertilization in the absence or presence of rLH supplementation, but a higher incidence of grade 1 to 2 embryos was observed when rLH was supplemented. CONCLUSION(S): After pituitary desensitization, there was an increase in the incidence of implantation, clinical pregnancy, and delivery rates in patients stimulated with rFSH supplemented with rLH.  相似文献   

19.
OBJECTIVE: We sought to assess the fertilization, implantation, and ongoing pregnancy rates with a minimal precycle and ongoing cycle monitoring protocol for in vitro fertilization and embryo transfer. STUDY DESIGN: Retrospective review was conducted of 103 consecutive cycles of fresh in vitro fertilization and embryo transfer from 1996 to 1998. Precycle screening included semen analysis without strict morphologic analysis, and hysterosalpingography-sonohysterography within the last year. Serum prolactin, serum thyroid-stimulating hormone, reactive plasma reagin, human immunodeficiency virus, rubella titer, blood type, hepatitis B surface antigen, and hepatitis C antibody testing was performed on all patients within 3 months of cycle initiation. Women > or =37 years old underwent clomiphene challenge testing. The monitoring protocol included the following: baseline transvaginal ultrasonography after 12 to 14 days of midluteal gonadotropin-releasing hormone agonist down-regulation to assess endometrial thickness and adnexal appearance, transvaginal ultrasonography for follicle evaluation at 7 and 10 days, serum estradiol assay if > or =20 follicles, quantitative beta-human chorionic gonadotropin 12 to 14 days after pre-embryo transfer, repeat quantitative beta-human chorionic gonadotropin 3 to 5 days later, and transvaginal ultrasonography for intrauterine gestational sac confirmation 7 to 9 days after the initial positive pregnancy test result. The dose of gonadotropin used remained constant unless the sonogram obtained on day 7 indicated a suboptimal response (<3 follicles each, with an average diameter of 10 to 12 mm) or hyperresponse (> or =15 follicles with an average diameter of 10 to 12 mm). RESULTS: The per embryo implantation rate (fetal cardiac activity) was 13.1%, and the live birth rate per 100 pre-embryo transfers was 31.5 for patients < or =40 years old. The average number of pre-embryos transferred was 3.1. The singleton pregnancy rate was 71%, and there were no multiple gestations greater than twins. The mean number of oocytes fertilized was 66%. There was 1 case of failed fertilization with intracytoplasmic sperm injection. There were two other cases of failed fertilization. One case of severe ovarian hyperstimulation occurred in spite of cryopreservation of all embryos. CONCLUSIONS: In vitro fertilization and embryo transfer can be accomplished with minimal precycle testing and ongoing cycle monitoring without compromising fertilization, implantation, and ongoing pregnancy rates. This results in reduced overall costs for couples.  相似文献   

20.
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