Ultrasonically guided oocyte recovery for in vitro fertilization: An improved method

Ultrasonically guided follicular aspiration is now routinely used for in vitro fertilization (IVF) in many centers. We present an improved method for oocyte recovery. One hundred nine consecutive patients with mechanical infertility submitted for IVF were included in the study. Superovulation was induced with human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG). Oocyte recovery was ultrasonically guided, the bladder filled with phosphate-buffered saline (PBS), and a cannula with trocar used for single percutaneous puncture. The aspiration needle was of 1.6 mm in internal diameter. When compared to published data using smaller-bore needles, it seems that this improved needle increased the number of oocytes recovered to a mean of 6.5 and the number of embryos replaced to a mean of 3.9 per patient, with a pregnancy rate of 20% per transfer.     

Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.     

Clomiphene-HMG ovarian stimulation in human in vitro fertilization and embryo transfer

In a program for in vitro fertilization and embryo transfer, laparoscopies for oocyte aspiration were performed in 40 cycles in 36 normally menstruating women with irreparable tubal diseases (IVF patients) who received clomiphene citrate (CC) and human menopausal gonadotropin (hMG). An intramuscular injection of human chorionic gonadotropin (hCG) was given to all patients after completion of follicular maturation. Fourteen cycles in 13 spontaneously ovulating women (control patients), also stimulated with CC and hMG, were adequately monitored to identify the appearance of the spontaneous luteinizing hormone (LH) surge. The follicular maturation was followed by daily ovarian ultrasonographic examination and serum estradiol estimations. Just before the LH surge the diameter of the leading follicle was 20.2 +/- 0.7 (mean +/- S.E.) mm and the serum estradiol concentration per follicle was 384.1 +/- 16.3pg/ml in the control patients. In the IVF patients the former was 20.6 +/- 0.3mm and the latter was 305.8 +/- 13.3pg/ml prior to hCG administration. When the relationship of follicular size to the rates of oocytes recovery, maturation, fertilization and cleavage was examined, larger follicles (3ml less than or equal to follicular fluid volume) showed good results. Of the 152 oocytes that were recovered from these IVF patients, 96 (63.2%) were fertilized and 79 (52.0%) cleaved. Three pregnancies resulted from 35 embryo transfers.     

Results of in vitro fertilization and embryo transfer by combined long-acting gonadotropin-releasing hormone analog D-Trp-6-luteinizing hormone-releasing hormone and gonadotropins

To avoid cancellation of in vitro fertilization (IVF) because of early luteinization, pituitary suppression by gonadotropin-releasing hormone (GnRH) was carried out in 111 cycles. D-Trp-6-luteinizing hormone-releasing hormone (LH-RH) microcapsules were administered intramuscularly at menstruation and menotropin (hMG) stimulation was started 19 days (mean) later. In 3 cycles (2.7%), only early luteinization occurred. The mean number of oocytes per cycle was 6.7, with a fertilization and cleavage rate of 50 and 95%, respectively. A mean of 3.4 embryos were transferred per cycle. The 111 cycles resulted in 34 clinical pregnancies, 41% per cycle with embryo transfer. The early abortion, multiple pregnancy, and ovarian hyperstimulation rates were 24, 18, and 11%, respectively. It is concluded that D-Trp-6-LH-RH/hMG cycles are associated with a very low occurrence of early luteinization, high number of oocytes and embryos, and a substantial incidence of ovarian hyperstimulation syndrome.     

The combination of follicle-stimulating hormone and human menopausal gonadotropin for the induction of multiple follicular maturation for in vitro fertilization

One hundred fifty-one cycles in 134 consecutive patients were stimulated with 150 IU of human urinary follicle-stimulating hormone (FSH) and 150 IU of human menopausal gonadotropin (hMG) on cycle days 3 and 4 and then with 150 IU of hMG daily for the purpose of multiple follicular development for in vitro fertilization (IVF). Seventy-three patients did not have a prior IVF attempt, and 61 patients in 78 cycles had prior IVF attempts at least once with their previous cycles stimulated with the same method and/or hMG and/or FSH. There was an average of three preovulatory oocytes retrieved per laparoscopy and a pregnancy rate of 27% per transfer cycle. The results were equally favorable in "new" and "old" patient cycles. The pregnancy rate increased with the transfer of two or more conceptuses of preovulatory origin. The multiple pregnancy rate, but not the abortion rate, increased with increased numbers of conceptuses transferred.     

IVF-ET周期中GnRH-a、FSH、hMG配伍方案的比较研究

目的:探讨IVF周期中采用不同促排卵方案时,卵泡液及血清中FSH、LH、E2水平的变化及对胚胎发育、受精、妊娠的影响;单用国产hMG促排卵的效果。方法:120例分成4组。测定卵泡液及取卵日血清中FSH、LH、E2水平,比较四种方案的取卵数、受精率、Ⅰ级、Ⅱ级胚胎形成率和每移植周期妊娠率。结果:四种促排卵方案的卵泡液和血清FSH、E2水平没有差别（P>0.05）,不同垂体降调节者,卵泡液和血清LH水平明显升高（P<0.0001）,四种促排卵方案的取卵数、受精率、优质胚胎形成率、移植周期妊娠率经统计学处理均无显著性差异。结论:卵泡液和血清中LH水平升高可能与应用垂体降调节有关,而与选择纯FSH还是hMG促排卵无关。轻度LH升高并不影响卵泡发育、卵子质量和以后的胚胎发育。IVF周期首选垂体降调节加FSH或FSH/hMG促排卵方案,单用hMG促排卵也可以作为选择。     

GnRH antagonist in older IVF patients. Retrieval rates and clinical outcome

OBJECTIVE: To determine if the use of a midcycle GnRH antagonist provides better clinical outcomes and lower cancellation rates in in vitro fertilization (IVF). STUDY DESIGN: We examined all patients older than 40 years undergoing IVF-embryo transfer cycles between January 1999 and December 2000. Prior to June 2000, controlled ovarian stimulation in women > or = 40 years was performed with follicle stimulating hormone (FSH)/human menopausal gonadotropin (hMG) only and no GnRH agonist or antagonist (group I). After June 2000, following the release of Ganirelix in the U.S., all women > or = 40 years were stimulated with FSH/hMG + Ganirelix (group II). Outcomes of IVF cycles prior to Ganirelix were compared to results after its introduction. RESULTS: Cancellation rates were significantly lower in group II (16%) as compared to group I (67%) (P < .05). In patients with oocytes retrieved, group II had a significantly higher number of recovered oocytes (7.7 +/- 0.8 vs. 5.3 +/- 0.7, P < .05). However, the number of embryos transferred, cumulative embryo scores, implantation rates and ongoing pregnancy rates did not differ significantly between groups. CONCLUSION: Although our results are preliminary, the addition of GnRH antagonist avoids ovarian suppression at the start of controlled ovarian hyperstimulation and prevents the premature LH surge at midcycle. Thus, more patients attempting IVF undergo oocyte retrieval, although clinical outcomes may not necessarily be improved.     

Absence of corpus luteum rescue by chorionic gonadotropin in women immunized with a contraceptive vaccine

OBJECTIVE: To investigate possible differences between using recombinant FSH (rFSH) and hMG for ovarian stimulation in IVF/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Parallel group design. Prospective, randomized clinical study. SETTING: A tertiary care infertility clinic. PATIENT(S): A total of 578 patients of our IVF/ICSI routine were recruited. INTERVENTION(S): Treatment with hMG was used for 282 patients (282 cycles), whereas 296 patients (296 cycles) were treated with rFSH. The number of cycles leading to an embryo transfer were 248 and 259, respectively. MAIN OUTCOME MEASURES: Primary: clinical pregnancy rate. Secondary: treatment days, total dose of gonadotropin administered, number of oocytes retrieved, number of mature oocytes, and embryo quality. RESULT(S):Of the cycles with embryo transfer, the pregnancy rates were 30.1% and 32.3% in the rFSH and the hMG groups, respectively. This difference is not statistically significant (P=0.798). Treatment with rFSH resulted in a significantly higher number of recovered oocytes compared with the hMG group but was also associated with a higher number of ampoules needed to reach the criterion for hCG administration. No significant differences were found with regard to the number of mature oocytes, the number of treatment days, and the embryo quality. CONCLUSION(S): In terms of the clinical pregnancy rate, no significant differences between the two stimulation regimens can be stated.     

Increasing the gonadotrophin dose in the course of an in vitro fertilization cycle does not rectify an initial poor response

OBJECTIVE: To evaluate the value of increasing the gonadotrophin dose after 5 days of controlled ovarian stimulation in IVF patients who show an initial poor response to stimulation. SUBJECTS AND METHODS: We identified all IVF cycles between January 1992 and March 1996 in which ovarian response after 5 days of controlled ovarian hyperstimulation (COH) with 225-300 IU per day of human menopausal gonadotrophins (hMG; Metrodin or Pergonal) was monitored by measurement of serum estradiol concentrations (n=596 patients). According to estradiol concentration, the daily dose of hMG was doubled or increased to 450 IU in 193 patients (group A) or maintained the same in 403 patients (group B). Further cycle monitoring was achieved using serial ultrasound and serum estradiol measurements. RESULTS: The two groups were age-matched. Group A patients experienced a higher cancellation rate despite having a higher mean number of hMG ampoules (59.5 versus 36.2) and a longer duration of stimulation (12.2 versus 10.8 days). They achieved lower levels of serum estradiol on days 9 and 10 of stimulation, produced a lower mean number of oocytes per retrieval (5.8 versus 8.9) and had a lower clinical pregnancy rate per cycle (8.3 versus 23.4%) compared to group B. All differences were statistically significant. CONCLUSION: The poor outcome of cycles with initial low response to COH appears not to be averted by doubling or increasing the hMG dose after 5 days of stimulation.     

Follicular stimulation for in vitro fertilization using pituitary suppression and human menopausal gonadotropins

Multiple follicular stimulation is a prerequisite to the efficient use of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). For some individuals, however, this stimulation may be difficult using standard superovulation protocols because of dominant follicle formation, suboptimal estradiol response, or premature luteinizing hormone surge. A group of such individuals with several previous failed attempts at superovulation were studied. Follicular stimulation was accomplished using a long-acting agonist of gonadotropin-releasing hormone (GnRH) for pituitary suppression followed by human menopausal gonadotropin (hMG) for follicular stimulation. Fourteen cycles (12 IVF, 2 GIFT) were completed in 12 individuals. There were no cycle cancellations. Mean number of prior cycle cancellations per patient was 3.1 +/- 0.4. Mean number of mature oocytes recovered was 3.9 +/- 0.5. Two pregnancies resulted. Pituitary suppression with a long-acting agonist of GnRH followed by hMG appears to be an effective adjunct to current superovulation regimens.     

Comparison between laparoscopically and ultrasonographically guided transvaginal follicular aspiration methods in an in vitro fertilization program in the same patients using the same stimulation protocol

Summary Oocyte recovery from 43 patients undergoing ultrasound-guided transvaginal oocyte retrieval was compared to a previous laparoscopic oocyte retrieval cycle from the same patient. Gonadotropin stimulation in both cycles was performed using the same protocol. There were no statistically significant differences in the mean day of oocyte retrieval or the mean daily estradiol level up to the day of oocyte retrieval between laparoscopic and transvaginal cycles. The total number of follicles aspirated per cycle, preovulatory oocytes aspirated per cycle, and number of concepti of preovulatory origin transferred per cycle were not statistically different. The number of immatue oocytes aspirated per cycle was statistically decreased in transvaginal retrieval cycles, which resulted in an increased total number of concepti transferred per transfer in laparascopic retrieval cycles. Twelve pregnancies resulted from the transvaginal retrieval cycles (27.9%), seven of which are ongoing or delivered. Ultrasound-guided transvaginal follicular aspiration yields results comparable to laparascopic retrieval in the same patients and should be the method of choice for oocyte pickup because of its many advantages.Presented in part at the ACOG Annual Meeting, Boston, 1988.     

An increased initial follicle-stimulating hormone/luteinizing hormone ratio does not affect ovarian responses and the outcomes of in vitro fertilization

The tenet that a combination of human follicle-stimulating hormone (hFSH)/human menopausal gonadotropin (hMG) improves follicular recruitment was assessed by randomly treating ovulatory women either with hFSH/hMG on days 3 and 4 of the cycle followed by two ampules of hMG daily or with a constant daily dose of 2 ampules of hMG. Estradiol (E2) levels on the day of human chorionic gonadotropin (hCG) and the mean number of mature, immature and atretic oocytes per cycle did not differ between the two groups. Likewise, fertilization, cleavage, and pregnancy rates were similar for the two treatments. When daily hormone levels were compared in 11 patients during two successive treatment cycles with both stimulation protocols, the temporal pattern of FSH accumulation was repeated in both cycles, but FSH levels were significantly higher when patients received hFSH/hMG. Nevertheless, during both cycles, E2 reached similar peak levels and the mean number of follicles per cycle on the day of hCG administration was not different. We conclude that routine use of hFSH/hMG does not improve the success of an in vitro fertilization (IVF) program and that higher FSH levels do not change the individuality of ovarian response in the same woman.     

超声下未成熟卵泡抽吸术治疗多囊卵巢综合征不孕的临床研究

目的　探讨超声下未成熟卵泡抽吸术(IMFA)对多囊卵巢综合征(PCOS)不孕患者卵巢窦卵泡计数及其内分泌功能的影响;观察IMFA后,应用人绝经期促性腺激素(hMG)促排卵治疗的效果、妊娠及并发症情况。方法　将71例PCOS不孕患者随机分为两组。组Ⅰ: 37例,穿刺前用少量hMG促排卵; 组Ⅱ: 34例,不用任何促排卵药物。在阴道超声引导下进行IMFA,检查穿刺后第2个周期患者的内分泌功能和卵巢基础窦卵泡计数,可连续2~3个周期进行穿刺。随后2组均用hMG常规促排卵治疗,随访其排卵及妊娠情况。结果　组Ⅰ进行了88个周期的穿刺治疗,经过2~3次穿刺后,睾酮水平、黄体生成素(LH )与卵泡刺激素(FSH)的比值均明显降低,与治疗前比较,差异有统计学意义(P<0. 01), 33例(89%, 33 /38)患者基础窦卵泡计数降至10个/卵巢以下。组Ⅱ进行了87个周期治疗,所有患者睾酮水平均显著降低,与治疗前比较,差异有统计学意义(P<0 01 ); 30例LH/FSH<2, 28例(82%, 28 /34)患者基础窦卵泡计数降到10个/卵巢以下。在IMFA之后, 诱发排卵时hMG用量组Ⅰ为(21±6)支,组Ⅱ(23±10)支,两组比较,差异无统计学意义(P>0 .05),在注射人绒毛膜促性腺激素(hCG)后均出现排卵, 组Ⅱ有2例发生轻度卵巢过度刺激综合征(OHSS)。连续促排卵治疗1 ~3个月后, 共36例(51% )     

CLINICAL ASSISTED REPRODUCTION: Improvement of IVF Outcome in Poor Responders by Discontinuation of GnRH Analogue During the Gonadotropin Stimulation Phase—A Function of Improved Embryo Quality

Purpose: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for IVF in patients with a previous poor response.Methods: Prospective case-control evaluation compared with same patient's previous performance. Thirty-six patients enrolled in an IVF program were treated in two consecutive cycles. The first with a standardized protocol utilizing mid-luteal administration of Nafarelin (N) 600 mcg/d continued throughout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard group). Patients with a poor response in the Standard cycle were treated in the subsequent cycle with N and hMG initially in a similar manner, then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and laboratory aspects of treatment were done in a similar fashion in both cycles, each patient acting as her own control.Results: Results were analyzed by paired t test. The change in each parameter in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and number of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28%, respectively), but insignificantly so. The percent of cleaving embryos was significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embryo morphology was improved by 22% (p = 0.02). The efficacy of gonadotropin treatment was enhanced in the N-stop cycle, as expressed by a 32.5% increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancelled in the standard protocol cycle. Of the 36 patients, 7 conceived in the N-stop protocol and 5 are ongoing pregnancies.Conclusion: Discontinuation of GnRH-a during ovarian stimulation for IVF has a beneficial, but not statistically significant, effect on both E2 and oocyte production. Embryo cleavage rates and morphology were significantly improved, this may be due to improved oocyte quality, which may have been responsible for achieving pregnancies. The efficacy of gonadotropin treatment was enhanced when GnRH-a was discontinued. These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is apparent especially in poor responder patients.     

Improvement of IVF outcome in poor responders by discontinuation of GnRH analogue during the gonadotropin stimulation phase--a function of improved embryo quality.

PURPOSE: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for IVF in patients with a previous poor response. METHODS: Prospective case-control evaluation compared with same patient's previous performance. Thirty-six patients enrolled in an IVF program were treated in two consecutive cycles. The first with a standardized protocol utilizing midluteal administration of Nafarelin (N) 600 mcg/d continued throughout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard group). Patients with a poor response in the Standard cycle were treated in the subsequent cycle with N and hMG initially in a similar manner, then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and laboratory aspects of treatment were done in a similar fashion in both cycles, each patient acting as her own control. RESULTS: Results were analyzed by paired t test. The change in each parameter in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and number of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28%, respectively), but insignificantly so. The percent of cleaving embryos was significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embryo morphology was improved by 22% (p = 0.02). The efficacy of gonadotropin treatment was enhanced in the N-stop cycle, as expressed by a 32.5% increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancelled in the standard protocol cycle. Of the 36 patients, 7 conceived in the N-stop protocol and 5 are ongoing pregnancies. CONCLUSION: Discontinuation of GnRH-a during ovarian stimulation for IVF has a beneficial, but not statistically significant, effect on both E2 and oocyte production. Embryo cleavage rates and morphology were significantly improved, this may be due to improved oocyte quality, which may have been responsible for achieving pregnancies. The efficacy of gonadotropin treatment was enhanced when GnRH-a was discontinued. These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is apparent especially in poor responder patients.     

Follicle stimulating hormone levels on cycle day 3 predict ovulation stimulation response

Aim To determine the value of basal follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E₂) levels on cycle day 3 in predicting the ovulation stimulation response in patients receiving exogenous gonadotropins for in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT).Methods One hundred eleven consecutive females with infertility due to various etiologies were investigated. Cycle day 3 serum levels of FSH, LH, and E₂ were determined prior to ovulation induction with a combination of clomiphene citrate and human gonadotropins. Follicular growth was monitored ultrasonically, and when appropriate, oocytes were recruited, counted, graded, and then used, as prearranged, for either IVF or GIFT. Basal hormone levels were compared to the peak E₂ concentration, the number of follicles aspirated, and the number of preovulatory oocytes recovered following drug therapy. Details of resulting pregnancies were also recorded.Results Patients with low basal FSH levels (<11.5 mIu/ml) yielded a higher mean number of preovulatory oocytes than those with high values (>11.5 mIu/ml), i.e., 6.7 oocytes per cycle vs 2.5 oocytes (P < 0.001). In the low group 97% of cycles yielded more than three fertilizable oocytes compared to 42% in the high group (P < 0.5). There were 16 term pregnancies (16%) in the low group and 1 (8.3%) in the high group. Basal LH and E₂ levels did not improve on the ability to distinguish between different populations of infertile females who responded differently to ovulation induction.Conclusion Cycle day 3 FSH levels are predictive of the ovulation response and probability of pregnancy in stimulated cycles and can be of value in patient selection and counseling in IVF and GIFT programs.     

Significance of the recovery of fractured-zona oocytes in an in vitro fertilization program

Recovery of fractured-zona oocytes (FZOs) from patients undergoing in vitro fertilization and embryo transfer (IVF/ET) has been previously reported. The present study was undertaken to determine the possible influence of different stimulation protocols and retrieval techniques on the incidence of FZOs, to analyze possible causes, and to evaluate the significance of FZOs in terms of IVF/ET results. Four hundred thirty-three cycles in which one or more FZOs were recovered (fractured-zona cycles; FZCs) and 1114 cycles in which FZOs were not obtained (intact-zona cycles; IZCs) were studied. A significantly higher number of follicles was aspirated in FZCs (7.16±3.5) than in IZCs (6.43±3.56), yielding significantly fewer immature oocytes in FZCs (1.58±1.93 vs 1.88±2.16) and a significantly higher number of atretic oocytes in FZCs (2.06±1.36 vs 0.73±1.21). No statistically significant difference was observed when the number of preovulatory oocytes obtained was compared. Nor were statistically significant differences observed as a result of either the type of stimulation [human chorionic gonadotropin (hMG), follicle-stimulating hormone (FSH), or a combination] or the aspiration technique utilized (laparoscopy vs ultrasonically guided puncture). Peripheral estradiol and progesterone and follicular fluid estradiol, progesterone, and androstenedione comparisons showed no significant differences. However, endocrine and morphologic findings (higher follicular androstenedione levels and estradiol/progesterone ratio, degenerated ooplasms) suggested some degree of late oocyte atresia, possibly due to slight hyperstimulation. In an experimental study, two healthy immature oocytes matured in vitro to the metaphase II stage showed degenerative changes in the ooplasm within 20 min after being subjected to mechanical zona pellucida (ZP) damage (mechanical fracture). We conclude that (1) the presence of fracturedzona oocytes in IVF cycles does not impair the pregnancy rates and (2) stimulation-derived oocyte accelerated maturation and subsequent trauma from aspiration determine the fracture of the ZP.     

Comparison of human menopausal gonadotropin, clomiphene citrate, and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization

Human menopausal gonadotropins (hMG) and clomiphene citrate (CC), either alone or in combination, are frequently used for in vitro fertilization (IVF) in an attempt to maximize the number of oocytes recovered and the number of embryos transferred. However, direct comparison of the relative efficacy of these protocols in the same institution has been limited. To evaluate this question, the authors examined the outcome of 304 consecutive women attempting IVF. One hundred eighty-one women received hMG, 42 received CC, and 81 received combination hMG/CC. The percentages of women undergoing laparoscopy were not different among the groups (69%, 71%, and 74%, respectively), nor were the rates of oocyte recovery (94%, 100%, and 100%). However, the percentage of women achieving oocyte fertilization (77%, 83%, and 93%) and embryo transfer (73%, 83%, and 90%) were significantly greater among those who had received hMG/CC stimulation. A comparison of hMG/CC with hMG and CC cycles revealed a statistically significant increase in the total number of developing follicles (4.5 +/- 0.3, 3.3 +/- 0.2, and 3.1 +/- 0.3, respectively; P = 0.0137), total oocytes recovered (4.1 +/- 0.3, 3.2 +/- 0.2, and 2.5 +/- 0.2; P = 0.0011), and embryos transferred (2.2 +/- 0.2, 1.4 +/- 0.2, and 1.4 +/- 0.2; P = 0.0013). However, there was no significant difference in the occurrence of ongoing pregnancies. Thus, in terms of the per-patient number of follicles, oocytes, and embryo transfers, combined hMG/CC stimulation appears to be superior to either hMG or CC alone. However, to date the combined regimen has not improved pregnancy rates.     

Outcome of in-vitro fertilization and embryo transfer after different regimens of ovarian stimulation

Sixty-eight women with bilateral tubal disease and fertile male partners underwent ovarian stimulation in 187 cycles for IVF after randomization to different ovulation induction regimens. All patients initially received 150 mg clomiphene citrate on days 5-9, this regimen induced sufficient stimulation in a smaller proportion of patients than the two other regimens used subsequently which included clomiphene in combination with human menopausal gonadotrophins (hMG). The fertilization rate was significantly reduced (52.4%) in oocytes collected from cycles stimulated with hMG alone (in a small sub-group of poor responders) compared with a rate of 64.1-66.4% in cycles stimulated with clomiphene alone or in combination with hMG. Embryonic development 44-48 h after insemination was significantly retarded when clomiphene alone was utilized but a higher proportion of fragmented or abnormal embryos was observed after stimulation with hMG alone. In 118 cycles embryo transfer was performed and 20 pregnancies were established, a pregnancy rate of 16.9%. All but two pregnancies were established when two or more embryos were transferred and when the embryos were at the 4-cell or later stage of development. The regimen of clomiphene in combination with 150 i.u. hMG resulted in significantly greater numbers of oocytes recovered and embryos available per patient for transfer than the other two regimens studied.     

The use of gonadotropin-releasing hormone analogs for in vitro fertilization: comparison between the standard form and long-acting formulation of D-Trp-6-luteinizing hormone-releasing hormone

The introduction of luteinizing hormone-releasing hormone (LH-RH) analogs into treatment schemes for the stimulation of ovulation has enabled the authors' in vitro fertilization (IVF) team to overcome two problems; they can now suppress spontaneous LH peaks and program their activity. Two hundred and five IVF cycles were investigated. The agent used was D-Trp-6-LH-RH, either in a sustained release formulation (112 cases, group 1) or in a standard form (93 cases, group 2). The quantity of human menopausal gonadotropin (hMG) necessary for adequate ovarian stimulation was much lower when the standard form of the analog was used. The number of oocytes recovered per puncture was greater in group 1 (7.6 compared with 5.1), but the difference was not significant when considering the number of embryos (2.4 compared with 2.1). The corrected pregnancy rate (with allowance for progressive introduction of freezing from the third embryo onwards) was identical in both groups. The authors conclude that systems in which LH-RH analogs are employed have a clear advantage over the classical treatment with clomiphene citrate/hMG, and that the immediate-action formulation of D-Trp-6-LH-RH is preferable.