The use of long-acting gonadotropin-releasing hormone agonist (GnRH-a; decapeptyl) and gonadotropins versus short-acting GnRH-a (Buserelin) and gonadotropins before and during ovarian stimulation for in vitro fertilization (IVF)

The efficiency of two ovarian stimulation protocols using different gonadotropin-releasing hormone agonists (GnRH-a) for in vitro fertilization (IVF) was examined and compared with human menopausal gonadotropin (hMG)-only stimulation. Fifty-four patients who had 57 aspiration cycles were treated with protocol 1, which consisted of long-acting GnRH-a D-Trp⁶ (Decapeptyl Depot) and hMG. Protocol 2 entailed intranasal administration of short-acting GnRH-a (Buserelin) and human menopausal gonadotropin (hMG) in 66 women, who underwent 70 aspiration cycles. Fifty-five patients who had 59 ovum pickups (OPU) treated with hMG only served as a control. No differences were observed in cycle parameters and hormonal concentrations among the three groups. The total clinical pregnancy rates per OPU for patients receiving protocols 1 and 2 were 12.3 and 27.1%, respectively (P<0.05). The pregnancy loss was significantly lower in protocol 2 than in protocol 1 (26.3 versus 71.4%;P<0.05). Our data show superiority of short-acting GnRH-a over the long-acting agents in achievement of pregnancy and its outcome, though neither was significantly different from the hMG-only protocol.     

Effect of clomiphene citrate on follicular and luteal phase luteinizing hormone concentrations in in vitro fertilization cycles stimulated with gonadotropins and gonadotropin-releasing hormone antagonist

OBJECTIVE: To investigate the effect that clomiphene citrate exerts on luteinizing hormone (LH) concentrations in gonadotropin/gonadotropin-releasing hormone (GnRH) antagonist cycles. DESIGN: Retrospective analysis. SETTING: Tertiary referral center. PATIENT(S): Two groups of patients undergoing in vitro fertilization (IVF) were compared. In group I, 20 patients were stimulated with clomiphene citrate (CC) in combination with gonadotropins and 0.25 mg of Cetrorelix (ASTA Medica AG; Frankfurt am Main, Germany) and in group II, 20 patients were stimulated with gonadotropins and 0.25 mg of Cetrorelix. INTERVENTION(S): Blood sampling was performed in the late follicular, periovulatory, early, mid, and late luteal phases. MAIN OUTCOME MEASURE(S): Luteinizing hormone (LH), estradiol, and progesterone. RESULT(S): LH levels were significantly higher in group I than in group II on all the days studied. Progesterone serum concentrations were significantly higher in group II in the early luteal phase, but not in the follicular or the middle and late luteal phases. CONCLUSION(S): LH concentrations are significantly higher in the follicular and luteal phases in cycles stimulated with CC, despite GnRH antagonist administration. This observation might have implications for the dose of GnRH antagonist needed to suppress LH in the follicular phase and questions the need for luteal-phase supplementation in cycles in which CC was used.     

Short-term use of gonadotropin-releasing hormone agonist (Leuprolide) for in vitro fertilization

A common problem encountered by in vitro fertilization (IVF) programs is the premature occurrence of the spontaneous lutenizing hormone (LH) surge during ovarian stimulation cycles. Administration of gonadotropin-releasing hormone agonists (GnRH-a) for 2 to 3 weeks produces a state of hypogonadotropic hypogonadism, thus allowing ovarian stimulation to proceed uncomplicated by a spontaneous LH surge. We have elected to treat seven patients with GnRH-a in a short-term protocol, with GnRH-a initiated on cycle day 3 along with exogenous gonadotropins. In this series, we found that the spontaneous LH surge was abolished, while ovarian responsiveness seemed to be improved. These results suggest that the initial surge of gonadotropins elicited by GnRH-a administration may enhance ovarian stimulation and that spontaneous LH surge is blocked when GnRH-a and exogenous gonadotropins are initiated concomitantly.     

High-dose follicle-stimulating hormone (FSH) ovarian stimulation in low-responder patients for in vitro fertilization

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.     

Ovarian stimulation for in vitro fertilization using pure follicle-stimulating hormone with and without gonadotropin-releasing hormone agonist in high-responder patients

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.     

Effectiveness of short pituitary suppression with gonadotropin-releasing hormone agonist leuprolide during induction of ovulation for in vitro fertilization

A short suppression regimen with daily 0.5 mg leuprolide commencing the first day of in vitro fertilization (IVF) cycles was evaluated in 10 women who previously underwent similar IVF cycle without suppression. Induction of ovulation, oocyte retrieval, incubation, and embryo transfer were similar in all the cycles. Assessment included the amount of human menopausal gonadotrpin (hMG) used, length of stimulation, serum estradiol and luteinizing hormone (LH) levels, number of oocytes retrieved and their quality, cleavage rate, and number of embryos. The results showed that when leuprolide was used, no endogenous LH surge was detected, and there was a significant increase in hMG injected, from 19.0±5.8 to 34.4±17 ampoules, and in estradiol, levels, from 1276±470 to 2618±1084 pg/ml (mean ± SD). In addition, there was an increase in the total oocytes retrieved from 54 to 94, their cleavage rate from 59 to 86%, and the number of embryos from 24 to 70 in the suppressed cycle. No deleterious effects were observed and there were two pregnancies in this group.     

Comparison of outcomes and direct cost between minimal stimulation and conventional protocols on ovarian stimulation in in vitro fertilization

AIM: To determine whether minimal stimulation with clomiphene and gonadotropin provides outcomes and direct costs comparable with those of a conventional GnRHa-gonadotropin stimulation protocol for infertile patients undergoing in vitro fertilization. METHODS: A non-randomized clinical trial was conducted from 1 July 1996 to 31 March 2003 at the Infertility and Assisted Reproductive Unit, Ramathibodi Hospital, Faculty of Medicine, Mahidol University, Thailand. A total of 192 patients were recruited of whom 96 cases underwent ovarian stimulated cycles with minimal stimulation protocol, and 96 controls underwent ovarian stimulated cycles with GnRHa-gonadotropin protocol, with cases and controls matched for age and infertility cause. RESULTS: The median patient age was 35 years. Endometriosis was the most frequent infertility cause (28.1%). The conventional GnRHa-gonadotropin protocol could give more oocyte numbers than the minimal stimulation protocol (7.3 +/- 4.9 vs 4.5 +/- 3.3 oocytes). The fertilization rate and cleavage rate were similar (73.4 +/- 31.9 and 84.9 +/- 32.6 in minimal stimulation protocol, 69.3 +/- 29.6 and 88.4 +/- 28.0 in GnRHa-gonadotropin protocol, respectively). The pregnancy rate per oocyte retrieval cycle in the GnRHa-gonadotropin protocol was similar to the minimal stimulation protocol. (13.1%vs 13.0%, P = 1.000). However, the cost per pregnancy of minimal stimulation protocol was less than that of GnRHa-gonadotropin protocol. (6021.95 US dollars for minimal stimulation protocol per pregnancy, 10,785.65 US dollars for GnRHa-gonadotropin protocol per pregnancy, P < 0.000). CONCLUSION: Minimal stimulation was less effective than conventional GnRHa-gonadotropin on the ovarian stimulation. However, the total costs of minimal stimulation were cheaper than the conventional GnRHa-gonadotropin protocol. The decreased costs of minimal stimulation justifies further evaluation of its role in the treatment of infertility in selected cases.     

Hyperbaric oxygen and ovarian follicular stimulation for in vitro fertilization: a pilot study

Our objective was to assess the safety and tolerability of hyperbaric oxygen therapy (HBO) as an adjunct to IVF therapy in women with a poor prognosis for pregnancy in a prospective observational pilot study. We conclude that HBO is well tolerated by women undergoing IVF treatment and that further study is required to determine whether this is an efficacious adjuvant therapy for women being treated by IVF.     

A prospective randomized comparison between long and discontinuous-long protocols of gonadotropin-releasing hormone agonist for in vitro fertilization

Objective: To investigate the efficacy of a discontinuous-long protocol in an IVF program.

Design: Prospective randomized study.

Setting: University hospital.

Patient(s): One hundred thirty-seven IVF cycles of 92 patients in an outpatient IVF program from April 1995 to December 1995.

Intervention(s): In the discontinuous-long protocol group (n = 68), GnRH agonist (GnRH-a) was administered from the luteal phase until cycle day 7, when pure FSH administration was begun. In the long protocol group (n = 69), GnRH-a was administered until the day before hCG administration.

Main Outcome Measure(s): Serum LH and ovarian steroid hormone levels, and IVF outcome.

Result(s): The period and the total dosage of hMG were increased in the discontinuous-long protocol group. Although the fertilization rate was similar under both protocols, the number of embryos transferred was smaller and the cancellation rate was higher in the discontinuouslong protocol group because of the greater failure of oocyte retrieval and fertilization. Serum E₂ levels in the late follicular phase were lower in the discontinuous-long protocol group.

Conclusion(s): Early discontinuation of GnRH-a is not beneficial because of its adverse effects on follicular development.     

Comparison of clinical outcomes among dual ovarian stimulation,mild stimulation and luteal phase stimulation protocols in women with poor ovarian response

This study aimed to determine whether consecutive ovarian stimulation in follicular and luteal phases within a single menstrual cycle (dual stimulation) is achievable and superior to conventional stimulation for poor ovarian responders (PORs). Data of 260 PORs were retrospectively collected and divided into three groups. Group A comprised of cycles with dual ovarian stimulation (n?=?76), which were divided into two subgroups (follicular [group A-F] and luteal phase stimulation [group A-L]); group B comprised of cycles with ovarian stimulation that was performed only in the luteal phase (n?=?52). Group C comprised of mild ovarian stimulation cycles (n?=?132). Baseline parameters were not different among the three groups. The numbers of oocytes and embryo obtained were less in group A-F than group B and C, while group A overall had significantly more oocytes and viable embryo retrieved than did group B and C. Group A-L consumed significantly less gonadotropin than group B, without compromising the number of retrieved oocytes and embryo. The pregnancy outcomes of transfer of embryo from different stimulation phases were similar. We conclude that dual ovarian stimulation protocol is effective and potentially optimal for PORs.     

Freeze-all embryo strategy in poor ovarian responders undergoing ovarian stimulation for in vitro fertilization

This retrospective study determined the efficacy of the ‘freeze-all’ embryo strategy in poor ovarian responders undergoing ovarian stimulation for in vitro fertilization (IVF). A total of 559 poor responders who met Bologna criteria between January 2012 and December 2014 were included in this study: 256 in the fresh embryo transfer group and 303 in the freeze-all group. Vitrification and warming of day 3 embryos were performed using the Cryotop method. The poor responders treated with fresh embryo transfer and those treated with freeze-all strategy showed similar live birth rates per cycle (12.1% vs. 16.2%, p?=?.172) and per transfer (15.9% vs. 20.9%, p?=?.182). Multivariate logistic regression analysis showed that maternal age at retrieval (odds ratio, 0.919; 95% confidence interval, 0.865–0.977; p?=?.006) and number of good-quality embryos transferred (odds ratio, 1.953; 95% confidence interval, 1.346–2.835; p?相似文献   

Spectrophotometric analysis of human follicular fluid with regard to in vitro fertilization (IVF) parameters,follicular protein,and hormone content

Purpose Our purpose was to investigate possible relationships with spectrophotometric absorbance (458-nm region) and biochemical variables in follicular fluid (FF) as well as in vitro fertilization (IVF) outcome.Methods This study included 227 normal ovulatory women undergoing oocyte retrieval for IVF. Blooduncontaminated fluid samples, identified by spectrophotometry, were investigated. Spectrophotometric absorbance of FF at 458 nm (n = 426), as well as hLH, FSH, PRL, hCG, testosterone, sialic acid, ₁-antitrypsin and plasminogen of selected fluids, was analyzed.Results Small-volume follicles (2 ml) were associated with higher absorbance profiles (P <0.05), when compared to volumes greater than 2 ml. Our data suggest that the presence or absence of an oocyte, the potential of an oocyte to fertilize or cleave, failed to show any relationship with maximum FF absorbance at 458 nm. Maximum absorbances were significantly lower in FF from patients who subsequently became clinically pregnant (P =0.039). No correlation between FF absorbances and biochemical parameters (P >0.15) were established. Conclusions Absorbance of clear FF at 458 nm should not be viewed as the single parameter to predict oocyte development in vitro.     

Comparison between follicular stimulation and luteal stimulation protocols with clomiphene and HMG in women with poor ovarian response

This retrospective study is to compare the follicular mild stimulation and luteal simulation protocols for poor responders undergoing in vitro fertilization (IVF). A total of 131 women were diagnosed as poor responders. Thirty-three women started ovarian stimulation in early-luteal phase and 98 women started in early follicular phase with 100?mg/d clomiphene citrate and 75–150?IU/d HMG. There were more oocytes retrieved (2.8?±?2.0 versus 2.0?±?1.2, p?0.05), more available embryos (1.8?±?1.4 versus 1.3?±?1.1, p?0.05) and top-quality embryos (0.9?±?0.9 versus 0.4?±?0.6, p?0.05), and reduced cycle cancellation rate (12.1% versus 30.6%, p?0.05) in luteal group than in follicular group. The clinical pregnancy (17.7%, 20.0% and 41.2%) and live-birth rates (10.78%, 20.0% and 29.4%) after transferring embryos obtained from luteal, follicular and mixed stages were comparable (p?>?0.05). For poor responders, luteal phase stimulation could be an option because of increasing the chance to obtain competent embryos and reducing the cycle cancellation rate.     

Premature luteinization during gonadotropin-releasing hormone antagonist cycles and its relationship with in vitro fertilization outcome

OBJECTIVE: To determine the prevalence and the effect of premature luteinization in GnRH antagonist IVF-ET cycles. DESIGN: Prospective observational study. SETTING: In vitro fertilization-embryo transfer (IVF-ET) program at the Instituto Valenciano de Infertilidad. PATIENT(S): Eighty-one infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH antagonist for IVF-ET. INTERVENTION(S): Gonadotropin-releasing hormone (GnRH) antagonist was administered from stimulation day 6. Serum P, E(2), and LH were determined on the day of hCG administration. MAIN OUTCOME MEASURE(S): Cycles were grouped according to serum P level on the day of hCG administration (<1.2 ng/mL or > or =1.2 ng/mL). Clinical pregnancy and implantation rates were determined. RESULT(S): The incidence of premature luteinization was 38.3%. Total recombinant FSH dose and stimulation days differed significantly between the groups. Pregnancy rate (25.8% vs. 54.0%) and implantation rate (13.8% vs. 32.0%) were significantly lower in the premature luteinization group. CONCLUSION(S): Premature luteinization during GnRH antagonist IVF-ET cycles is a frequent event that is associated with lower pregnancy and implantation rates. Progesterone elevations are not related to serum LH levels and may reflect the mature granulosa cell response to high FSH exposure.     

A comparative study of dydrogesterone and micronized progesterone for luteal phase support during in vitro fertilization (IVF) cycles

The aim of the present study was to compare the efficacy, tolerability and patients’ satisfaction after the use of oral dydrogesterone with vaginal micronized progesterone for luteal-phase support (LPS) among infertile women undergoing in vitro fertilization (IVF). A total of 210 women (aged 20–40 years old) with a history of infertility, who underwent controlled ovarian stimulation for fresh intra-cytoplasmic sperm injection-embryo transfer cycles, were included in the study. Consequently, they were randomized to receive LPS with dydrogesterone 20?mg twice daily (n?=?96) or micronized progesterone 400?mg twice daily at the day of oocyte retrieval (n?=?114). The clinical success rate (31% versus 33%; p?=?0.888), miscarriage rate (5.0% versus 3.0%; p?=?0.721), ongoing pregnancy rate (30.0% versus 30.0%; p?=?1.000), implantation (22.0% versus 24.0%; p?=?0.254) and multiple pregnancy rate (5.30% versus 7.20%; p?=?0.394) were comparable among the two groups. Serum progesterone levels were significantly lower among the patients receiving dydrogesterone than the control group (13.62?±?13.83?ng/ml versus 20.66?±?18.09?ng/ml; p?=?0.001). However, there was no statistically significant difference regarding the patients’ satisfaction (p?=?0.825) and tolerability (0.790) between the two groups. Our results showed that oral dydrogesterone (40?mg/day) is as effective as vaginal micronized progesterone considering its clinical outcomes and patients’ satisfaction and tolerability, for LPS among women undergoing IVF.     

Support of the luteal phase in in vitro fertilization programs: Results of a controlled trial with intramuscular proluton

There is disagreement among in vitro fertilization (IVF) programs as to the need to administer exogenous progesterone to support the luteal phase of patients undergoing embryo transfer after IVF. We examined the effect on pregnancy rates of Prolution, 50-mg daily injections given on days 7–16 following oocyte recovery, in 186 women undergoing IVF treatment using a combined stimulation regime of clomiphene and human menopausal gonadotropin (hMG). One group was deliberately selected for treatment on the possible criterion of lutealphase deficiency and two other groups were randomly selected into a treatment and a control group. No effect on pregnancy rate was noted in any of these groups. These results indicate that extension of the luteal phase with exogenous progesterone is unlikely to have a significant effect on increasing the pregnancy rate in IVF programs using similar treatment regimes.     

Ovarian stimulation with gonadotropin-releasing hormone (GnRH) analogue improves the in vitro fertilization (IVF) pregnancy rate with both transvaginal and laparoscopic oocyte recovery

The relative impact of ovarian stimulation protocal and oocyte retrieval technique on success rates of in vitro fertilization program was studied in 200 patients. Sixty-three patients received gonadotropin-releasing hormone analogue (GnRHa) with human menopausal gonadotropin (hMG), and 137 received hMG only. The GnRHa+ hMG protocol resulted in higher pregnancy rates than the hMG-only protocol (19.0 vs 9.5%, respectively; P<0.01) despite a lower cleavage rate. Oocyte retrieval was performed via laparoscopy in 100 patients and transvaginally in 100 patients. The number of oocytes recovered per cycle was 6.1±3.9 with laparoscopy and 7.0±3.1 transvaginally. Pregnancy rates were similar for both retrieval techniques (13 and 12%, respectively). A breakdown of these results showed that the advantage for the GnRHa+hMG protocol was not affected by the oocyte retrieval technique. A comparison of simultaneous blood and follicular fluid pH measured every 10 min during laparoscopy and transvaginal oocyte recovery revealed a constant decline in follicular fluid pH during laparoscopy, while no changes were observed during the vaginal procedure. We conclude that the improvement in in vitro fertilization results during the period of our study is due primarily to the introduction of GnRHa+hMG protocol rather than the method of oocyte retrieval.