Combination clomiphene citrate/human menopausal gonadotropin stimulation protocols for in vitro fertilization-embryo transfer

Various protocols have been utilized for stimulation of multiple ovarian follicles in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). Previous studies have suggested that the combination of clomiphene citrate (CC) and human menopausal gonadotropins (hMG) is superior to either CC or hMG alone in terms of follicular development, oocyte recovery, and embryo transfer. However, no significant increase in viable pregnancy rates has been reported with any of the protocols. This report examines five different CC/hMG protocols. While differences were seen in terms of serum estradiol response and fertilization rates of mature oocytes among the various protocols, no significant differences were found in terms of follicular development, oocyte recovery, embryo transfer, or pregnancy. The pregnancy rate in IVF-ET appears unaffected by variations in the dose and timing of CC and hMG in a combination protocol.     

Efficacy of the urinary hemagglutination test (Higonavis) and enzyme immunoassay (Ovustick) in detection of the spontaneous luteinizing hormone surge in an in vitro fertilization/gamete intrafallopian transfer (IVF/GIFT) program

Fifty-eight treatment cycles in an in vitro fertilization/gamete intrafallopian transfer (IVF/GIFT) program were studied to compare the efficacy of two urinary methods, hemagglutination test (Higonavis) and enzyme immunoassay (Ovustick), in detection of spontaneous luteinizing hormone (LH) surge. If an isolated rise in urinary LH level was taken as indicative of LH surge, the false-positive rate was 36.7% for Higonavis and 10.2% for Ovustick. The difference was statistically significant (P<0.001). If only a sustained rise in urinary LH was taken to indicate LH surge, the false-positive rate was 6.1% for Higonavis and 0% for Ovustick. In the seven cycles with a spontaneous plasma LH surge, there was a positive correlation between the plasma LH levels and the two urinary assay methods in six cycles (85.7%). Compared to plasma LH, there was a mean delay of 17.4 hr by the Higonavis test and 15.6 hr by the Ovustick test. If a sustained rise in urinary LH levels was taken as indicative of LH surge, both methods are quite accurate but the Ovustick appeared to be more specific.     

Fertilization of supernumerary oocytes following gamete intrafallopian transfer (GIFT): Correlation with outcome of GIFT treatment

In the course of 280 consecutive gamete intrafallopian transfer (GIFT) attempts, supernumerary oocytes in excess of those transferred were inseminated in vitro. Pregnancy resulted in 31.1% of patients following the GIFT treatment. The overall in vitro fertilization (IVF) rate of supernumerary oocytes was significantly higher in those who became pregnant (41.2%) than in patients who did not (34.9%). However, the failure to fertilize any supernumerary oocytes was not significantly different between those becoming pregnant (27.6%) and those in whom the treatment failed (37.3%). Failure to fertilize any supernumerary oocytes in vitro was of a higher rate if suboptimal sperm preparation was used or if only one oocyte was left over for in vitro insemination following the GIFT treatment. We concluded that the in vitro fertilization rate was higher in the pregnant group, but the total failure to fertilize or the fertilization of any supernumerary oocytes does not predict the outcome of GIFT. Embryos resulting following fertilization of excess oocytes may be cryopreserved for subsequent use.     

An 18-month survey of infertility treatment by in vitro fertilization,gamete and zygote intrafallopian transfer,and replacement of frozen-thawed embryos

An 18-month survey of infertility treatment by in vitro fertilization (IVF) and related procedures at the Centre for Reproductive Medicine of the Vrije Universiteit Brussel is described. During this period, 1326 treatment cycles were started in patients with long-standing infertility and 1135 oocyte retrievals were performed in 771 different patients. IVF and embryo transfer (ET) after laparoscopic (N=793) or ultrasonically guided (N=342) ovum pickup, gamete intrafallopian transfer (GIFT;N=284), or zygote intrafallopian transfer (ZIFT;N=15) combined with IVF as well as the replacement of cryopreserved embryos yielded an overall pregnancy rate of 21.8% per started cycle. Echographic and laparoscopic oocyte retrieval gave similar results except for a higher fertilization rate after echographic-guided retrieval. For in vitro fertilization and embryo transfer an overall pregnancy rate of 26% per transfer was obtained. For GIFT and ZIFT the pregnancy rates were, respectively, 27.8 and 46.7% per replacement. For each procedure onethird of the pregnancies aborted. After the replacement of frozen and thawed embryos, during a natural cycle, a significantly lower fetal loss was observed.     

Effects of clomiphene citrate and leuprolide acetate on luteal-phase hyperprolactinemia during ovarian stimulation with menopausal gonadotropins

Hyperprolactinemia, a known modulator of reproductive function, occurs commonly in women undergoing ovarian stimulation with human menopausal gonadotropins (hMG). Clomiphene citrate (CC) and gonadotropin releasing hormone analogues (GnRHa), when administered during the luteal phase, attenuate the hyperprolactinemic response to hMG. We asked whether follicular-phase administration of CC and GnRHa, as employed clinically in women undergoing ovarian stimulation forin vitro fertilization or gamete intrafallopian transfer, would alter the incidence and severity of hMG-induced luteal-phase hyperprolactinemia. Seventy-five percent of all patients had at least one luteal prolactin level >25 ng/ml, and 40% had mean luteal-phase prolactin levels >25 ng/ml. The incidence of hyperprolactinemia was similar in pregnant and nonpregnant cycles. The incidence of hyperprolactinemia was similar for both the GnRH agonist-treated group and those given clomiphene citrate. The increase in mean luteal prolactin levels over the follicular-phase baseline level was significantly greater in the CC-treated group (P=0.03). This was due to the significant suppression of follicular-phase baseline prolactin levels in patients receiving CC. We conclude that neither CC nor GnRHa administration in the follicular phase prevents lutealphase hyperprolactinemia in women undergoing ovarian stimulation with hMG.     

Combined gonadotropin releasing hormone agonist/human menopausal gonadotropin therapy (GnRH-a/hMG) in normal,high, and poor responders to hMG

Patients who failed to conceive after gonadotropin stimulation in in vitro fertilization treatment were classified into normal, high, or poor responders. They were routinely offered another cycle with a combination of a gonadotropin releasing hormone agonist and gonadotropin therapy (in order to evaluate whether this combined therapy could improve their response). The gonadotropin-induced cycle was compared with the combined therapy cycle. With the combination treatment, in the normal responders the phase of ovarian stimulation was significantly (P<0.001) prolonged, and the number of follicles and oocytes collected (5.7±0.7 vs 3.1±0.4) was increased, without any change in serum estradiol level compared to the control cycle. In high responders the number of oocytes was not modified by the combined treatment compared with the control cycle. However, serum estradiol level was significantly (P<0.005) decreased. The combined therapy did not modify any parameter of response in poor responders. We conclude that the response to combined agonist/gonadotropin therapy is dependent on the patient's own basal response. No improvement in response was expected in poor responders.     

人绝经期促性腺激素联合氯米芬或来曲唑用于多囊卵巢综合征患者促排卵疗效比较

的探讨人绝经期促性腺激素（HMG）＋氯米芬（CC）、HMG和来曲唑（LE）＋HMO对多囊卵巢综合征（PCOS）患者宫腔内供精人工授精的治疗效果。方法将2007年12月-2008年5月期间在我中心就诊的114例PCOS妇女的114个宫腔内人工授精（AID）周期分为3组：CC＋HMG周期组38个周期，HMG周期组38个周期，LE＋HMG周期组38个周期。分析比较3组的年龄、血清T水平、绒毛膜促性腺激素肌肉注射日（HCG日）平均卵泡直径（MFD）≥14mm的卵泡（成熟卵泡）个数、平均卵泡E2水平、子宫内膜厚度、HCG日单优势卵泡发育成熟百分率、HMG用量和周期妊娠率。结果CC＋HMG组、HMG组和LE＋HMG组患者年龄和血清T水平比较，差异无显著性（P〉0．05），CC＋HMG组HCG日成熟卵泡个数为（2．9±1．6）个，明显多于其他两组[HMG组为（1．6±1．0）个，LE＋HMG组为（1．9±1．2）个]，差异有显著性（P〈0．05），而内膜厚度较其他两组薄，差异有显著性（P〈0．05），HMG组与LE＋HMG组HCG日成熟卵泡个数和子宫内膜厚度比较，差异无显著性（P〉0．05）。3组HCG日单优势卵泡发育成熟百分率分别21．05％、78．95％和52．63％，差异有显著性（P〈0．05）。CC＋HMG组、HMG组和LE＋HMG组HMG用量分别为（4．89±1．59）支和（9．88±4．59）支、（9．68±4．67）支（75IU／支），CC＋HMG组与后两组比较，差异有显著性（P=0．00）。HMG组、LE＋HMG组HMG用量比较，差异无显著性（P〉0．05）。3组的周期妊娠率分别为36．84％、39．48％和31．57％，差异无显著性（P〉0．05）。结论HMG促排卵周期更易得到单优势卵泡发育成熟；CC＋HMG促排卵HMG用药量最少；CC＋HMG、HMG和LE＋HMG均可获得满意的周期妊娠率。     

The duration of pituitary suppression by means of intranasal gonadotropin hormone-releasing hormone analogue administration does not influence the ovarian response to gonadotropin stimulation and success rate in a gamete intrafallopian transfer (GIFT) program

The aim of the study was to compare the ability to prevent endogenous luteinizing hormone interferences, ovarian response, and success rate between two groups of patients undergoing GIFT procedures and treated with the same stimulatory protocol but with a different timing in the administration of the gonadotropin hormone-releasing hormone analogue (GnRH-a). The former underwent a concomitant administration of gonadotropin and analogue; the latter started stimulation only after the achievement of complete hypogonadotropinism. The analogue was always given intranasally and stimulation was identical in the two groups. Our results showed that (1) prevention of premature luteinization is obtained with both approaches and (2) no significant difference in terms of length of stimulation, gonadotropin doses, ovarian response, and success rate was recorded between the two groups.     

Addition of a gonadotropin releasing hormone (GnRH) antagonist and exogenous gonadotropins to unstimulated in vitro fertilization (IVF) cycles: Physiologic observations and preliminary experience

Purpose To describe our preliminary experience with the addition of a GnRH antagonist (Nal-Glu) and exogenous gonadotropins (follicle stimulating hormone; FSH) to unstimulated IVF cycles.Method Seven spontaneously ovulatory women underwent eight unstimulated IVF cycles at our institution. They were treated with a single dose of Nal-Glu, 50 g/ kg, or with a combination of Nal-Glu, 50 g/kg, and exogenous FSH, 150–300 IU, during the late follicular phase of spontaneous cycles. They then received 10,000 IU of human chorionic gonadotropin (hCG) to time accurately follicle aspiration in unstimulated IVF cycles.Results Two women underwent three cycles with Nal-Glu alone on the day of hCG administration. One pregnancy resulted. Five women underwent five cycles with 3 to 6 days of daily Nal-Glu and FSH. Four of these cycles resulted in aspiration after the FSH dose was increased to 300 IU. Nal-Glu and FSH allowed continued development of the dominant follicle without the occurrence of luteinizing hormone (LH) surge.Conclusions (1) Nal-Glu alone given 18 hr prior to hCG did not interfere with continued follicle viability or with the attainment of pregnancy. (2) Simultaneous Nal-Glu and FSH allowed for continued growth and development of the dominant follicle without the occurrence of an LH surge. (3) This preliminary experience confirms the feasibility of this novel approach, which may ultimately enhance the efficacy of unstimulated IVF cycles by eliminating premature ovulation and maximizing control of gonadotropin delivery to the developing follicle.Presented at the 39th Meeting of The Society for Gynecologic Investigation, San Antonio, Texas, March 18–21, 1992.     

Basal serum pituitary hormone levels and outcome of in vitro fertilization utilizing a flare nasal gonadotropin releasing hormone agonist and fixed low-dose follicle-stimulating hormone/human menopausal gonadotropin regimen

Day 2 serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are prognostic indicators in treatment with in vitro fertilization (IVF) and FSH is especially useful in predicting the ovarian response to superovulation.     

In vivo fertilization procedures in infertile women with patent fallopian tubes: A comparison of gamete intrafallopian transfer,combined intrauterine and intraperitoneal insemination,and controlled ovarian hyperstimulation alone

This prospective study was undertaken to evaluate the relative efficacy of three in vivo methods of assisted fertilization in 150 infertile women with patent fallopian tubes: gamete intrafallopian transfer (GIFT), combined intrauterine and direct intraperitoneal insemination (IUI + DIPI), and controlled hyperstimulation (COHS) alone. The clinical pregnancy rate was highest in the IUI/DIPI and GIFT groups: IUI/DIPI, 29.3%; GIFT, 28.6%; and COHS, 8.9%. We believe that controlled ovarian hyperstimulation combined with IUI and DIPI is a good alternative to GIFT.     

Ultrasonic assessment of endometrial changes in stimulated cycles in an in vitro fertilization and embryo transfer program

Four distinct patterns in the ultrasonic appearance of preovulatory endometrium can be identified and described in patients undergoing stimulated cycles in an in vitro fertilization program. Ultrasonically, this endometrial response can be seen as a quantitative change in thickness and a qualitative change in gray-scale appearance or reflectivity. The application of this additional parameter of endometrial assessment together with the conventional measurement of follicular diameter as a means of optimally timing oocyte collection has been associated with a reduction in the preoperative ovulation rate from 10.9 to 3.2%, an increase in the fertilization rate from 59.2 to 82.5%, and in a pregnancy rate per embryo transfer of 20.5% in our program without the use of hormonal assays.