Luteinizing response to human chorionic gonadotropin does not predict outcome in gonadotropin releasing hormone agonist-suppressed/human menopausal gonadotropin-stimulated in vitro fertilization (IVF) cycles

Objective The purpose of this study was to determine if early luteinizing potential in gonadotropin releasing hormone agonist (GnRH-a)-suppressed/human menopausal gonadotropin (hMG)-stimulated IVF cycles is predictive of cycle outcome.Design, Patients The study was a prospective evaluation of 41 women beginning a GnRH-a-suppressed/hMG-stimulated IVF cycle.Setting The in vitro fertilization program of a tertiary care institution was the study setting.Main Outcome Measures The main outcome measures were (1) estradiol (E₂) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration and the following day and (2) the ovarian response to ovulation induction and clinical outcome.Results Ten of the 41 women achieved a clinical pregnancy (24.4%). There was no significant difference in progesterone (P) levels on the day of or the day following hCG administration between the pregnant and the nonpregnant groups. Both groups exhibited a significant rise in P level in response to hCG. There was no significant difference in E₂ levels on the day of hCG between the two groups. The serum E₂ did not rise significantly in response to hCG in either group. Patients who became pregnant had significantly more oocytes retrieved, fertilized, cleaved, and transferred.Conclusions Clinical response and outcome in GnRH-a-suppressed/hMG-stimulated IVF cycles are not predicted by early luteinizing potential as indicated by the response of E₂ or P to hCG.Presented at the 7th Annual World Congress of in Vitro Fertilization, Paris, France, June 30–July 3, 1991.     

Preliminary experince with a combination of clomiphene and variable dosages of menopausal gonadotropins for enhanced follicular recruitment

A combination of clomiphene citrate and human menopausal gonadotropin was employed for enhanced follicular recruitment in an in vitro fertilization program. All patients received 50 mg of clomiphene and 1 ampule of human menopausal gonadotropin daily from cycle day 5 through cycle day 9. Follicular monitoring was begun on day 10 using a combination of ultrasound measurement of follicular size and number and determination of peripheral estradiol levels. Based on the size and number of follicles, the peirpheral levels of estradiol, and the rate of follicular growth and increase in estradiol, human menopausal gonadotropin was continued at a dosage of 1 to 3 ampules/day through the day of human chorionic gonadotropin administration. Human chorionic gonadotropin was administered on the evening of the day the largest follicle reached or exceeded 20 mm in mean diameter if the estradiol levels had been rapidly rising or reaching a plateau and had exceeded a minimal level of 300 pg/ml. Using this protocol, 30 of 33 patients underwent laparoscopy, 29 patients had successful oocyte recovery, and 23 patients underwent embryo replacement, with the establishment of six clinical pregnancies.     

Follicular-phase response in two clomiphene-human menopausal gonadotropin regimes for an in vitro fertilization program

Two clomiphene-human menopausal gonadotropin regimes were assessed for our in vitro fertilization and embryo replacement (IVF and ER) program since September 1983. Clomiphene, 50 mg bd, was taken from day 2 for 5 days. Human menopausal gonadotropin (hMG) was given from day 6; for the first regime, 75 IU/day was given for the first 3 days, and for the second, 150 IU/day. The subsequent dosages were dependent on the estradiol response. There were 9 cases for the first regime and 10 cases for the second. The mean number of hMG ampoules given was 16.5 and 19.25, respectively. The number of follicles seen on ultrasound was 3.0±0.5 and 3.4±1.2 (mean±SD), respectively. There was no statistical difference in the estradiol response up to the day of laparoscopic ova recovery for the two regimes. However, a spontaneous luteinizing hormone (LH) surge was observed in 4 of 9 cases in the first group and 6 of 10 cases in the second group. When a comparison was made between cases that had a spontaneous LH surge and cases that were given human chorionic gonadotropin (hCG), there was a higher estradiol level on the day of the laparoscopy in the hCG group with the lower hMG regime (P<0.05). There were no other differences. Our small series shows a 52.6% incidence of spontaneous LH surge with clomiphene-hMG. Hence such stimulated regimes can result in a high proportion of spontaneous LH surges; this may be an index of satisfactory endocrinological control in spite of an increase in the number of follicles.     

Comparison between Highly Purified-FSH and hMG for Superovulation in Women undergoing in vitro Fertilization

Objective: to assess the efficacy of highly purified follicle stimulating hormone (HP-FSH) compared to human menopausal gonadotrophin (hMG) in in vitro fertilization (IVF).Design: open, prospective, randomized parallel group, comparative, multicentre study.Setting: one private and one public institution.Patient: infertile population undergoing in vitro fertilization.Outcome of interest: ovarian response to drugs: birth rate.Results: increased number of follicles, oocytes and embryos in HP-FSH group and comparable birth rates.Conclusions: use of HP-FSH in IVF offers similar success rates to hMG. Subcutaneous administration makes HP-FSH simpler for both patients and medical staff.     

The day of initiation of human menopausal gonadotropin stimulation affects follicular growth in in vitro fertilization cycles

The attainment of synchronous follicular development in human menopausal gonadotropin/human chorionic gonadotropin-stimulated cycles for in vitro fertilization (IVF) continues to be a perplexing problem. Two regimens of follicle stimulation for IVF cycles were, therefore, compared. Twenty-nine patients commenced human menopausal gonadotropin (hMG) therapy on day I of the menstrual cycle (Group I), while 30 women received hMG from the third day of the cycle (Group II). The hMG therapy was tailored to the individual patients's response, based on ultrasonographic measurements of follicular size and serum estradiol (E₂) levels. Both groups of patients received a mean of 19.6±1.4 ampules of hMG over a mean of 6.1±0.2 days. The pattern of serum E₂ and progesterone levels in the periovulatory and luteal phase was not affected by the day of initiation of hMG therapy, although Group I patients demonstrated lower (P<0.05) E₂ levels on the 2 days prior to human chorionic gonadotropin (hCG) administration. In terms of follicle growth, Group II follicles consistently demonstrated a significantly (P<0.01,x ² test) larger proportion of medium- and large-sized follicles compared to Group I follicles on almost all of the days when ultrasonographic measurements were taken. In addition. Group II follicles demonstrated an earlier shift (day—1) to the larger follicles than Group I follicles (day 0). Significantly (P<0.001) more oocytes were recovered per uspirated follicle in Group II patients, but the fertilization rate per oocyte was greater (P<0.003) for Group I oocytes. Nevertheless, pregnancy rates did not differ between the two groups. It is suggested that a difference between the two groups of patients in the quantity or quality of gonadotropin receptor sites in the early part of the follicular phase may account for both the diminished E₂ production in the follicular phase and the persistent depressed follicular growth in Group I patients.     

Hypersensitization to human menopausal gonadotropins with anaphylactic shock syndrome during a fifth in vitro fertilization cycle

Conclusion Allergic reactions to therapies with human urinary-derived gonadotropins are of a low incidence. They may, however, have serious consequences as reported in our case study. In our opinion, they are probably related to the presence of copurified urinary proteins. One might hypothesize that highly purified and/or recombinant human gonadotropins will reduce this incidence yet further in the future.     

体外受精-胚胎移植中暂时性高催乳素血症对妊娠的影响

目的探讨在体外受精与胚胎移植(IVF-ET)中,注射人绒毛膜促性腺激素(HCG)日血清催乳素(PRL)浓度对妊娠的影响。方法回顾性分析2005年10月至2008年3月期间127个体外受精与胚胎移植周期的资料。结果在控制性卵巢刺激(COS)中,按注射HCG日血清催乳素浓度不同分4组,依次为<30ng/mL(A组),≥30～<60ng/mL(B组),≥60～<90ng/mL(C组),≥90ng/mL(D组)。体外受精与胚胎移植的种植率分别为13.68%、24.16%、15.90%、2.86%;临床妊娠率分别为25.00%、47.17%、29.41%、7.69%。各组的种植率及临床妊娠率差异有统计学意义(χ2检验,P值分别为0.018和0.019)。进一步进行两两比较,HCG日PRL≥90ng/mL(D组)的种植率及妊娠率明显较PRL水平≥30～<60ng/mL(B组)低,差异有统计学意义(P值分别为0.005和0.009)。结论控制性卵巢刺激后血清催乳素浓度较基础水平明显升高,导致暂时性高催乳素血症。当HCG注射日血清催乳素明显升高(≥90ng/mL)时,体外受精与胚胎移植的种植率及临床妊娠率明显下降。对控制性卵...     

Selection of ovarian stimulation protocol is related to IVF treatment outcome in women 35 years of age and older

Purpose The aim of this study was to assess if the woman's age influenced IVF treatment outcome when a long GnRHa-hMG or a CC-hMG ovarian stimulation protocol was used. Two hundred women were included in the study, 100 women under the age of 35 and 100 women 35 years of age and older (mean 31.8 years and 36.7 years respectively). In the younger group as well as in the older group 50 women were stimulated according to a GnRHahMG protocol and 50 women received a CC-hMG regimen.Results Significant differences between stimulation protocols were found in the older group for the mean numbers of oocytes recovered (4.7 vs 3.0), preembryos obtained (3.2 vs 2.0) and replaced (2.3 vs 1.7), as well as pregnancy (30 % vs 10 %) and delivery (24 % vs 4 %) rates per replacement.Conclusion It is concluded that women over 35 years of age seem to have a more favorable outcome of IVF treatment when using a long GnRHa-hMG protocol compared with CC-hMG, while this difference was not as obvious and lacking statistical significance under the age of 35.     

In vitro fertilization and embryo transfer: An individualized approach to ovulation induction

Because of the inherent marked individual responsiveness to ovulatory stimulating agents, a highly individualized approach to ovulation induction for in vitro fertilization has been utilized. The starting time for medication was varied according to the previous mean cycle length. The dose of clomiphene citrate was adjusted to the body weight. The dose and duration of both clomiphene and human menopausal gonadotropin (hMG) were adjusted as early as treatment day 5 in accordance with the ultrasonic findings. The day of human chroionic gonadotropin (hCG) administration was varied according to a combination of ultrasonic findings and plasma estradiol levels. This approach resulted in a mean retrieval of four oocytes per laparoscopy, 75% of which were mature, a fertilization rate of 78%, and a pregnancy rate of 14% of laparoscopies.     

The need to step up the gonadotropin dosage in the stimulation phase of IVF treatment predicts a poor outcome

Purpose It is a common practice to increase the gonadotropin dose during ovarian stimulation when the estradiol (E₂) rise is found to be inadequate. The prognostic impact of the use of this step-up regimen on the outcome of the affected in vitro fertilization (IVF) cycle is the subject of this study. Methods This is a retrospective analysis of IVF cycles in a series of consecutive patients who required an increase in the gonadotropin dosage during the stimulation phase because of inadequate E₂ rise. Controls consisted of patients in whom the dose was not increased. After 4 days of stimulation, the gonadotropin dosage was increased if E₂ levels failed to rise by 70% every 2 days. Outcome was defined in terms of maximum E₂ level, number of follicles at aspiration, number of oocytes obtained, fertility rate, and pregnancy rate and was compared in study and control patients. Pregnancy was defined by sonographic demonstration of cardiovascular activity. Results One hundred forty-five patients were analyzed. A stepup regimen was used in 35 patients (24.1%). Patients who required the step-up dosing had significantly lower peak E₂ levels (1373 vs 1828 pg/ml; P < 0.005), fewer follicles measuring greater than 16 mm (7.2 vs 9.7; P < 0.003), and fewer oocytes recovered (8.3 vs 11.2; P < 0.009). The fertilization rate (67.6 vs 64.2%) was not significantly different. The pregnancy rate (8.5 vs 32.7%; P < 0.004) was significantly lower in the group requiring the stepup regimen. Conclusions The utilization of a step-up regimen during an IVF treatment cycle is a predictor of a poor outcome for the specific IVF cycle. As this information is available before retrieval, consideration of cycle cancellation may be appropriate.     

Pregnancy Rate in IVF Rescue in High Responders to Human Menopausal Gonadotropin

Purpose: In vitro fertilization had been previously suggested by us as a means of rescue for patients with imminent ovarian hyperstimulation syndrome (OHSS) during treatment with human menopausal gonadotropin (hMG). We evaluated the pregnancy rate of rescued IVF cycles. Methods: During the years 1994–1995, women treated with hMG and at risk of developing OHSS were referred to our IVF unit. Their estradiol level was above 1500 pg/ml, and eight or more follicles were observed by ultrasonography In all the patients. These high responders were offered the option to undergo ovum aspiration. We report the pregnancy rate in this group of patients. Results: Thirty-nine women were referred to our unit for rescue IVF. Two were uneligible due to high progesterone concentrations. Thirty-seven women underwent ovum pickup and 32 had embryo transfer. The clinical pregnancy rate was 40% (13/32). Only two women had clinical OHSS. Conclusions: We suggest that rescue IVF may be considered in hMG cycles of high responders with imminent OHSS. Rescue IVF offers a high rate of conception, avoids high-order multiple pregnancy, and appears not to increase the risk of OHSS in these women.     

Serum and follicular fluid (FF) estradiol (E2) levels in ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles after pituitary suppression

Initaial hope that ovarian hyperstimulation syndrome (OHSS) would be less likely to occur after pituitary suppression with gonadotropin releasing-hormone agonists (GnRH-a) has not been substantiated. GnRH-alhuman menopausal gonadotropin (hMG) protocols often lead to OHSS with markedly elevated circulating estradiol (E₂) levels in susceptible patients. This study was undertaken to determine whether or not intrafollicular E₂ secretion is increased in these cases. Fifty-two in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) conception cycles treated with GnRH-alhMG were included in the study. GnRH-a, leuprolide, 0.5 mg, was administered subcutaneously from day 20 of the preceding cycle and the ovaries were stimulated with hMG, 75-225 IU bid intramuscularly, followed by human chrionic gonadotropin (hCG), 5000 IU. Twenty cycles (Group I) were associated with moderate or severe OHSS and 32 cycles (Group II) did not result in OHSS. E₂ was measured in the serum on the day of hCG (day 0), on the day of oocyte retrieval (day 2), and at midluteal phase (days 6–8), as well as in the follicular fluid (FF) using a solid-phase direct RIA. Mean serum E₂ was significantly higher at all three sampling times in Group I (OHSS) than in Group II. Both the number of follicles and the number of oocytes were also significantly higher in Group I. Mean (±SD) FF E₂ concentrations in both groups were similar (367±109 and 364±188) in follicles >15 mm in diameter but were increased in follicles 15 mm in diameter in OHSS (479±111) versus non-OHSS (230±32) patients. It appeared that OHSS was a function of an increased number of stimulated follicles as well as a result of altered steroidogenic function at the follicular level.     

Levels of oxytocin-like activity and progesterone in follicular fluid from in vitro fertilization cycles

Oxytocinlike immunoreactivity, estradiol, and progesterone were measured in follicular fluid collected during oocyte collection in an in vitro fertilization program in which clomiphene citrate was used to stimulate follicular development. Follicles which yielded morphologically normal embryos after fertilization of the oocyte had oxytocin concentrations ranging from <10 to 600 ng/liter. Oxytocin concentrations did not differ between follicles from 12 pregnancy cycles (median, 169; N=21 and follicles from 12 nonpregnancy cycles (median, 110; N= 18). Oxytocin concentrations were correlated negatively with progesterone concentrations (Spearman's rank correlation coefficient r=–0.50; P=0.001). In cycles with some follicles having progesterone concentrations <10 and some >10 mol/liter, oxytocin concentrations were higher in the less progestogenic follicles in 15 of 16 cases.     

Implantation,abortion, and birth after in vitro fertilization using the natural menstrual cycle or follicular stimulation with clomiphene citrate and human menopausal gonadotropin

The incidence of pregnancy and abortion was analyzed in 1679 patients having embryos replaced after oocyte recovery and in vitro fertilization in order to alleviate their infertility. In these patients, 364 pregnancies were achieved and 108 abortions occurred. Patients were treated either on their natural cycle, having a spontaneous luteinizing hormone (LH) surge to induce ovalation, or after ovarian stimulation using clomiphene citrate alone or in combination with human menopausal gonadotropin (hMG). The data were assessed in relation to the numbers of embryos replaced, the follicular stimulation and ovulation induction regime used; the dose of gonadotropins and the dose of antiestrogens, and the age of the patient. The most successful treatment for the number of live births per laparoscopy was the use of clomiphene citrate in combination with human menopausal gonadotropin followed by human chorionic gonadotropin (hCG) to induce follicular maturation and ovulation. This treatment produced a significantly higher (P<0.001) number of patients with multiple embryos (86.5%). There was no significant effect on pregnancy or abortion with alow (<400-mg) or high (400-mg) dose of clomiphene. The total dose of gonadotropins used did not influence the incidence of pregnancy or abortion. The use of hCG with hMG induced a significant (P<0.01) positive effect on the incidence of pregnancy. The incidence of pregnancy showed a progressive decline with increasing age but there was a highly significant (P<0.01) increase in the incidence of abortion with increasing age. With increasing numbers of embryos replaced, up to three, the incidence of deliveries increased. The most successful follicular stimulation regime and the replacement of three embryos produced about 25% of the patients delivering normal healthy babies after embryo replacement.     

Scheduling GnRH antagonist cycles by a short course of oral estradiol administration during early follicular phase: a comparative study with non-scheduled cycles

Abstract

This hypothesis generating study investigated whether GnRH antagonist cycles can be scheduled by a short course of oral estradiol administration during the follicular phase without impairing treatment outcome. Thirty-five women who underwent follicular phase estrogen scheduling (ES) of GnRH antagonist cycles were retrospectively matched for age and number of prior failed cycles with 35 women who underwent unscheduled GnRH antagonist cycles. ES group was given 6?mg/day estradiol orally from cycle day 2 until (including) one day before the scheduled start of stimulation. Gonadotropins were started on cycle days 2–3 in the control group. Flexible GnRH antagonist protocol was employed in both groups. ES group received estradiol for a median of 5 days. Total gonadotropin consumption was similar but one more GnRH antagonist injection was required in the ES group. Endometrial thickness on the day of hCG injection was increased in the ES group (12 versus 10?mm, p?<?0.01). Number of oocytes, metaphase II oocytes and transferred embryos were similar. Embryo implantation rates were 44.8% versus 34.4% (p?=?0.3), and clinical pregnancy rates were 48.6% versus 37.1%, (p?=?0.33) in the ES and control groups, respectively. All women in the ES group had oocyte retrieval and embryo transfer within the desired period.     

Serum and follicular fluid sex hormone-binding globulin in stimulated and unstimulated cycles

Background It is wellknown that sex hormone-binding globulin (SHBG) concentrations in the follicle are relatively low in comparison with the corresponding estradiol (E₂) levels, which are extremely high. A direct comparison of these data in stimulated and unstimulated cycles, as well as the relationship of SHBG with testosterone (T) and E₂ in serum and follicular fluid (FF), is assessed.Methods SHBG was measured in serum and FF in 42 cycles stimulated by GnRH agonists and gonadotropins and in 15 unstimulated cycles. The levels of SHBG were compared to the corresponding total estradiol and total testosterone concentrations. The analyzed FFs of 42 women, 12 of whom conceived, were randomly selected from 90 patients participating in an in vitro fertilization program. Mature oocytes were retrieved from all follicles from which FFs were analyzed.Results Markedly elevated SHBG was found in both the serum and the FF of stimulated cycles compared to unstimulated cycles. In contrast, serum T and E₂ were significantly higher in induced than in unstimulated cycles, while there was no significant difference in FF T or E₂ between the two groups of cycles. No correlation was found between serum and FF SHBG in either stimulated or unstimulated cycles. In stimulated cycles, only in FF, SHBG was significantly correlated with both E₂ and T. In unstimulated cycles, no correlation was found between SHBG and either one of the corresponding steroids either in serum or in FF.Conclusions The fraction of non-SHBG bound, biologically active sex steroids may be lower in the FF of stimulated than that of unstimulated cycles.Presented in part at the VIIIth World Congress on in Vitro Fertilization and Alternate Assisted Reproduction, Kyoto, Japan, 1993.     

Endogenous luteinizing hormone release using human menopausal gonadotropins for in vitro fertilization

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.     

Delayed embryo implantation following in vitro fertilization and embryo transfer (IVFET)

Purpose: Our goal was to compare serum human chorionic gonadotropin (hCG) levels in singleton pregnancies achieved following IVFET with those achieved following spontaneous conception. Results: The mean serum hCG level of patients who became pregnant following IVFET lagged 1.5 days behind that of patients who became pregnant spontaneously. Conclusions: The use of gonadotropin releasing hormone analogue as part of the stimulation protocol leading to egg retrieval and IVFET results in a delay in embryo implantation.