Experiences with the first 100 consecutive pregnancies achieved after in vitro fertilization and embryo transfer at the University Women's Hospital in Erlangen

As of March 31, 1985, 100 clinical pregnancies have been achieved since the program for extracorporeal fertilization was started in Erlangen. 531 (71%) of 768 follicular punctures resulted in an embryo transfer. The overall pregnancy rate is 13% with regard to the total number of laparoscopies and 19% with regard to the number of embryo transfer. The most effective stimulation proved to be the pure hMG regimen. Employing this protocol, we have achieved a clinical pregnancy rate after IVF and ET of 32% during the last 6 months. Oocyte recovery related to the number of patients is 97%, with laparoscopy being superior to ultrasonically guided puncture. The success rate is appreciably affected by both the number of transferred embryos and the atraumatic transfer technique. We question the rationale of supporting the luteal phase.     

Comparison of outcome of clomiphene citrate/human menopausal gonadotropin/cetrorelix protocol and buserelin long protocol--a randomized study.

This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium. One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were randomized into two groups. Sixty women were stimulated with the CC/hMG/cetrorelix protocol (cetrorelix group) and 60 received the buserelin long protocol (buserelin group). Fewer oocytes were recovered in the cetrorelix group than in the buserelin group (mean +/- standard deviation (SD): 11.1 +/- 4.0 vs. 17.3 +/- 5.8, p < 0.001); however, the percentages of metaphase II, metaphase I and germinal vesicle oocytes were similar between the two groups. Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group (mean +/- SD: 2600.58 +/- 1189.11 vs. 3293.46 +/- 1221.49 pg/ml, p = 0.006), but the endometrial thickness was similar. The implantation rates (19.2% vs. 17.7%) and the pregnancy rates (41.7% vs. 40.0%) were similar between groups. The ampoules (mean +/- SD: 18.9 +/- 3.0 vs. 38.9 +/- 12.2, p < 0.001) and injections (mean +/- SD: 6.8 +/- 1.1 vs. 15.7 +/- 3.1, p < 0.001) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group. No patients in either group developed a premature luteinizing hormone surge. The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates.     

Good results of milder form of ovarian stimulation in an in vitro fertilization/intracytoplasmic sperm injection program.

In a prospective study, we compared two protocols of ovulation stimulation, the clomiphene citrate and human menopausal gonadotropin (hMG) versus D-triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist and hMG in 324 couples having their first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) program, in terms of pregnancy rates and cost-effectiveness of drugs used. The GnRH agonist/hMG group was characterized by a greater mean number of ampoules of hMG used (31.7 versus 10.2), a larger number of oocytes collected (10.4 versus 4.2), and a larger number of embryos obtained (5.8 versus 2.9). With the policy of transferring only two of the best quality embryos, the mean number of embryos replaced were comparable (1.8 in clomiphene citrate/hMG and 1.9 in GnRH agonist/hMG group). The percentage of patients reaching embryo transfer was lower in the clomiphene citrate/hMG than in the GnRH agonist/hMG group (84.1% versus 93.1%, respectively). However, the combined results of the IVF and ICSI procedure in terms of pregnancy rate, both per patient and per embryo transfer were better, though not significantly in the clomiphene citrate/hMG than in GnRH agonist/hMG group (25.0% and 29.7% versus 23.7% and 25.5%, respectively). Similarly, the implantation rate was better (19.0% versus 13.5%, respectively). With the use of clomiphene citrate/hMG, a fivefold less costly drug regimen, we obtained pregnancy rates equivalent to those gained using GnRH agonist/hMG in our IVF/ICSI program.     

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.     

Prospective, randomized, comparative study of leuprorelin + human menopausal gonadotropins versus ganirelix + recombinant follicle-stimulating hormone in oocyte donors and pregnancy rates among the corresponding recipients.

AIM: To compare the clinical pregnancy rate in recipients of oocytes from donors treated with leuprorelin + human menopausal gonadotropins (hMG) with that obtained when the donors were treated with ganirelix + recombinant follicle-stimulating hormone (rFSH). The secondary aim was to compare the donors' response to the two treatments. METHOD: A prospective, randomized, comparative study was conducted between January 2005 and November 2006 in a private hospital. Donors were randomized to receive a long protocol of leuprorelin + hMG (group DI) or ganirelix + rFSH (group DII). Their respective recipients were randomized to group RI or group RII, respectively. RESULTS: The characteristics of the donors were similar in both groups. More cycles were cancelled in group DI than in group DII (28.1% vs. 2.5%; p < 0.05). Compared with donors in group DII, the donors in group DI required a significantly higher dose of gonadotropins (2794 +/- 957 U vs. 1777 +/- 1043 U; p < 0.05) and more days of stimulation (11.7 +/- 2.3 vs. 9.5 +/- 1.5; p < 0.05); they also yielded fewer oocytes (15.0 +/- 6.1 vs. 17.9 +/- 8.6; p < 0.05). There were no differences in the characteristics of the recipients, in the fertilization rate or in the number of embryos transferred. The quality of transferred embryos was better in group RI (8.0 +/- 1.2 vs. 7.5 +/- 1.6; p < 0.05), and this group also achieved a better pregnancy rate per embryo transfer than did group RII (62.3% vs. 48.4%; p < 0.05). CONCLUSIONS: Treating oocyte donors with leuprorelin + hMG produces among recipients a greater probability of clinical pregnancy per embryo transfer than when donors are treated with ganirelix + rFSH; however, more cycles are cancelled and the former treatment is more unpleasant for donors.     

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.     

Factors influencing pregnancy rates with a combined clomiphene citrate/gonadotropin protocol for non-assisted reproductive technology fertility treatment

OBJECTIVE: To determine the effectiveness of a combined clomiphene citrate/gonadotropin protocol in a general infertility population and to evaluate factors influencing pregnancy rates obtained with this protocol. DESIGN: A retrospective chart review. SETTING; University-based infertility clinic. PATIENT(S): Two hundred forty-eight patients undergoing 658 cycles of minimal stimulation (MS) protocol from 1996-2000. INTERVENTION(S): Patients underwent treatment with clomiphene citrate and gonadotropin, often followed by intrauterine insemination. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Overall, the clinical pregnancy rate was 7.1% per cycle (n = 248 patients and 658 cycles). The age range of the patients was 24-47 years (mean +/- SD = 36.5 +/- 4.9) with 8.7% noted to have ovulatory dysfunction. Pregnancy rates varied significantly (P<.05) with patient age (9.3% in women <40 years vs. 2.4% in women > or =40), duration of infertility (9.0% in women with < or =3 years of infertility vs. 2.2% in women with >3 years of infertility) and number of follicles produced during stimulation (9.1% in women with > or =3 follicles vs. 4.6% in women with <3 follicles). CONCLUSION(S): The effectiveness of the MS protocol in a general infertility population with a predominantly ovulatory status is much less than that previously reported in a younger patient population with a significant rate of ovulatory dysfunction. This protocol does not appear to lead to pregnancy rates higher than that reported for clomiphene citrate/intrauterine insemination (IUI) cycles. The clinical pregnancy rates using a minimal stimulation protocol are particularly compromised in women over 40, those with a longer duration of infertility or those who produce few follicles during stimulation.     

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

Summary. 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.     

Superovulation with buserelin and gonadotropins dramatically improves the success rate of intrauterine insemination with husband's washed semen

The purpose of this study was to determine the effectiveness of intrauterine insemination with husband's washed semen during stimulated cycles using a combined treatment of GnRH agonist (buserelin) and gonadotropins. 47 infertile couples were studied; 25 couples were treated with buserelin and gonadotropins (study group) and 22 (control group) received clomiphene citrate alone. Indications for treatment, in both groups, were male subfertility, cervical factor or unexplained infertility. For sperm preparation, the same swim up technique in both groups was used. In the study group, 15 pregnancies were achieved (pregnancy rate: 60%) whereas only 5 pregnancies were achieved in the control group (pregnancy rate: 22.7%) (p less than 0.01). The pregnancy rate per cycle was 17.6 and 4.8 respectively (p less than 0.01). The mean number of follicles per cycle (+/- SEM) was 3.6 +/- 0.2 and 1.7 +/- 0.07, respectively (p less than 0.0005). Comparing successful and unsuccessful cycles a difference was observed only among the levels of 17 beta E2, both per cycle and per follicle/cycle (1075 +/- 165.4 vs 721 +/- 57.6 and 319.8 +/- 42.6 vs 219.9 +/- 17.8; p less than 0.01 and p less than 0.0005 respectively). The authors conclude that intrauterine insemination with washed sperm during stimulated superovulatory cycles is a successful mode of therapy in all couples with infertility not associated with anatomic damage of the adnexa or with chronic anovulation.     

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.     

In vitro fertilization management and results in stimulated cycles with spontaneous luteinizing hormone discharge

During a period of 14 months, in an in vitro fertilization program, 97 ultrasonically guided follicular punctures were performed in women with premature spontaneous luteinizing hormone (LH) discharge (group I) and 217 in women with a normal LH value who received human chorionic gonadotropin injection as a surrogate LH surge (group II). All cycles were stimulated by clomiphene citrate plus human menopausal gonadotropin. In group I, oocytes were not recovered in 35% of punctures, compared with only 21.2% in group II (P less than 0.02). In cycles in which the serum 17 beta-estradiol (E2) levels was less than 1200 pg/ml and the number of follicles greater than or equal to 14 mm diameter monitored was less than three, 69% of punctures in group I and 36.7% of punctures in group II failed to yield oocytes. We suggest that patients stimulated in this way who have a spontaneous LH discharge with an E2 value of less than 1200 pg/ml and less than three follicles 14 mm in diameter present should not proceed to follicular puncture.     

The prognostic importance of the number of oocytes retrieved and estradiol levels in poor and normal responders in in vitro fertilization (IVF) treatment

A low response to ovarian stimulation in in vitro fertilization poses a unique therapeutic challenge. Gonadotropin-releasing hormone agonists (GnRHa) have been suggested as a modality for treatment of this condition. In this study, we analyzed the results of 880 in vitro fertilization treatment cycles with respect to modality of ovarian stimulation, degree of hormonal response, and number of oocytes retrieved. In patients with estradiol (E ₂ )levels less than 501 pg/ml on the day of human chorionic gonadotropin administration, 27% pregnancy rate was achieved with clomiphene citrate (CC) combined with human menopausal gonadotropin (hMG), compared to 15.1% (P <0.005) with hMG alone and 20.8% (NS) with GnRHa and hMG. Pregnancy rates were not lower in these patients compared to patients with higher estradiol levels in the different stimulation protocols, but pregnancy rates were significantly lower in cycles during which three or fewer oocytes were retrieved, compared to those in which four or more oocytes were retrieved (10.8 vs 23.8%; P <0.0005). In low-retrieval cycles pregnancy rates actually decreased with increasing levels of estradiol. Our results indicate that the number of oocytes retrieved is a better prognostic parameter than E ₂ levels in predicting the outcome of in vitro fertilization treatment and that GnRHa in the long protocol do not seem to be superior to CC combined with hMG for the treatment of poor responders.     

The use of clomiphene citrate/human menopausal gonadotrophins in conjunction with GnRH antagonist in an IVF/ICSI program is not a cost effective protocol

OBJECTIVE: To evaluate the cost effectiveness of a clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/GnRH antagonist protocol versus a long-acting GnRH agonist/hMG protocol. PARTICIPANTS AND METHODS: One hundred eighty nine couples having their first trial of ICSI for male factor infertility were divided into two groups. Group I (no = 33) received CC 100-150 mg/day for five days starting from day 2 of the cycle and 150 IU of hMG/day on days 6-10. GnRH antagonist (Centrorelix) 0.25 mg/day was started when the leading follicle reached 16 mm in the absence of an LH surge. Group II (no = 156) received 0.1 mg Deacapeptyl/day as our standard long protocol. RESULTS: Clinical pregnancy was observed in 8 out of the 33 cases in group I (24%) while in group II, 92 out of 156 achieved clinical pregnancy (59%), the difference was statistically significant (P = 0.019). The cost of medications/cycle was estimated to be 1110+/-492 E.P in group I, while it was 1928+/-456 E.P. in group II. However, the total cost per pregnancy was 19653 EP in group I and 10047 EP in group II. CONCLUSION: The use of the clomid/hMG/antagonist protocol is not a cost effective strategy and should not be recommended in IVF-ICSI cycles.     

A comparison of clomiphene/menotropins and D-Trp6-LH-RH/menotropins cycles of IVF-ET in the same patients.

Pituitary suppression by long-acting D-Trp6-LH-RH and concomitant hMG ovarian stimulation for in vitro fertilization and embryo transfer (ET) has been used in 19 patients who previously failed to conceive, following ovarian stimulation by clomiphene citrate and hMG. When available, up to five embryos were transferred. Compared with the previous CC/hMG cycles, D-Trp6-LH-RH/hMG cycles were associated with significantly more embryos (P less than .002), lower follicular-phase basal LH levels (P less than .05), and a higher early luteal progesterone level (P less than .05). Following D-Trp6-LH-RH/hMG cycles, 11 patients had a clinical pregnancy. The multiple pregnancy rate was 18% and the abortion rate, 18%. Thirty percent of the cycles (6/20) were associated with the ovarian hyperstimulation syndrome. These promising results warrant a further trial of D-Trp6-LH-RH-hMG stimulation.     

Evaluation of leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins for in vitro fertilization or gamete intrafallopian transfer

A prospective randomized trial was conducted to compare the efficiency of two ovarian stimulation protocols for in vitro fertilization-embryo transfer or gamete intrafallopian transfer. Protocol 1 consisted of clomiphene citrate and human menopausal gonadotropin (hMG) with 55 cycles of 42 patients being evaluated. Protocol 2 had 38 cycles of 34 patients receiving a gonadotropin-releasing hormone agonist (GnRH-a) and hMG. The incidence of a spontaneous luteinizing hormone surge was 38.2% in protocol 1 and 0% in protocol 2. Both protocols had a similar cancellation rate. The total clinical pregnancy rates per oocyte retrieval for patients receiving protocol 1 and protocol 2 were 19.5% and 10.3%, respectively. The difference was not statistically significant. Therefore, as first-line ovulation induction agents, it cannot be concluded that either protocol demonstrates a clear superiority over the other and further trials of the GnRH-a/hMG combination are indicated.     

In Vitro Fertilization with Low-Dose Clomiphene Citrate Stimulation in Women Who Respond Poorly to Superovulation

Purpose: Our experience with IVF using low-dose clomiphene citrate for stimulation in non- and poor responders was reviewed and the treatment outcomes with the previous controlled ovarian stimulation cycles in which hMG and GnRH agonist were used were compared. Methods: The treatment outcome in 11 non- and 20 poor responders having 30 and 53 clomiphene citrate IVF treatment cycles, respectively, were compared with the treatment outcome in the previous long-protocol buserelin/hMG cycles. Results: The clinical pregnancy rates per oocyte collection achieved in the first clomiphene citrate cycle in non (9.1%)- and poor (10%) responders were comparable to those achieved by poor responders (11.9%) who had buserelin/hMG using the long protocol. Although the numbers were small, a similar pregnancy rate could still be achieved in poor responders up to the third attempt using clomiphene citrate. Conclusions: IVF using long-protocol buserelin/hMG is more successful than using clomiphene citrate stimulation. However, this advantage may not be significant in those women with a previous poor response to buserelin/hMG. It is suggested that for such poor responders, three attempts of IVF in a clomiphene citrate cycle may offer a viable therapeutic alternative before reverting to more stressful, expensive, and time-consuming treatment.     

Immaturity and aneuploidy in human oocytes after different stimulation protocols

OBJECTIVE: To study immaturity and aneuploidy in human oocytes after two different stimulation protocols. DESIGN: Retrospective. SETTING: Outpatient IVF clinic/laboratory. PATIENTS: One hundred forty-three patients of whom 65 were stimulated with clomiphene citrate (CC)/human menopausal gonadotropin (hMG) and 78 were stimulated with gonadotropin-releasing hormone agonist (GnRH-a)/hMG. Only patients with at least one oocyte unfertilized were included in this study. RESULTS: Stimulation with GnRH-a/hMG, as compared with CC/hMG stimulation, resulted in larger numbers of oocytes (P less than 0.00001), a higher fertilization rate (P less than 0.02), and oocyte retrieval at a later average cycle day (P less than 0.000005). Cytogenetic findings of immaturity were observed in 33.9% of unfertilized oocytes after CC/hMG stimulation, compared with only 17.8% after GnRH-a/hMG stimulation (P less than 0.0005). Aneuploidy findings were the same for both groups. CONCLUSION: In GnRH-a/hMG stimulation, oocytes approach the normal day of ovulation more closely. This may allow for better oocyte maturation and higher fertilization and pregnancy rates.     

Randomized trial of three luteinizing hormone-releasing hormone analogues used for ovarian stimulation in an in vitro fertilization program.

OBJECTIVE: To determine if biochemical differences in luteinizing hormone-releasing hormone analogues (LH-RH-a) have a clinical influence, we studied three of these molecules: buserelin acetate (group B), triptorelin (group T), and leuprorelin (group L). DESIGN: Clinical trial. SETTING: In Vitro Fertilization (IVF) Center. PATIENTS: Two hundred forty-six patients, undergoing their first IVF attempt, were randomly allocated to one group. The analogues were used in a long protocol for ovarian stimulation in an IVF program. RESULTS: After 15 days of LH-RH-a therapy, the follicle-stimulating hormone level was lower in group B (2.9 +/- 1, 4.3 +/- 1.7, 4.8 +/- 2.1 UI/L for B, T, and L groups, respectively; P less than 0.001), although no difference was found in LH and estradiol (E2) levels. After follicular growth stimulation by human menopausal gonadotropins (hMG), E2 level was significantly lower in B group (1,799 +/- 1,101, 2,440 +/- 1,298, 2,137 +/- 1,044 pg/mL for B, T, and L groups, respectively; P less than 0.01), as well as the E2 level per hMG ampule (67 +/- 51, 97 +/- 61, 82 +/- 49 for B, T, and L groups respectively; P less than 0.01). The pregnancy per stimulated cycle rate was not significantly different among the groups. CONCLUSIONS: These results suggest that LH-RH-a could act not only on the pituitary but also on the ovaries. Moreover, these data suggest that buserelin acetate could be preferentially used for high responders and triptorelin for poor responders.     

Minimal stimulation protocol for use with intrauterine insemination in the treatment of infertility

OBJECTIVE: To determine whether minimal stimulation with clomiphene and one injection of 150 IU of human menopausal gonadotrophin (hMG) provides pregnancy rates comparable with those in a conventional full hMG stimulation protocol for infertile patients undergoing intrauterine insemination (IUI). METHODS: A prospective study was carried out at the Infertility Clinic of a teaching institute and tertiary care referral center in Chandigarh, India. Two hundred couples with either unexplained infertility or ovulatory dysfunction cases who ovulated with clomiphene citrate (CC) but failed to conceive were offered ovarian stimulation with CC and hMG along with IUI for 420 cycles. Pregnancy rate, medication and monitoring cost were compared between minimal and conventional stimulation protocols. RESULTS: There was no difference in the couples of the two stimulation protocols regarding their age, duration and type of infertility as well as cause of infertility. Number of ampoules of hMG and monitoring costs were significantly higher in the full hMG stimulation cases whereas pregnancy rate was comparable in both protocols. CONCLUSION: Minimal stimulation appears to be an effective protocol in cases of unexplained infertility undergoing intrauterine insemination. Reduced cost and minimal monitoring is appealing to patients and the clinician.     

The use of the GnRH analogue buserelin for IVF--does it improve fertility?

OBJECTIVE--To determine the effect of a short course of the GnRH analogue buserelin and human menopausal gonadotrophin (hMG), for ovarian stimulation in our IVF programme, on reproductive endocrinology and pregnancy rates compared with conventional clomiphene citrate and hMG treatment. DESIGN--Prospective randomized allocation to one of two ovulation stimulation regimens. SETTING--Fertility clinic. SUBJECTS--373 infertile couples with various factors associated with their subfertility. All the women were less than 46 years of age and had normal menstrual cycles. INTERVENTION--The first group (n = 151) was given clomiphene citrate (CC) from days 2-6 of the menstrual cycle and hMG from day 5 onwards (CC/hMG). The second group (n = 222) was given buserelin from days 1-3 and hMG from day 2 (buserelin/hMG). MAIN OUTCOME MEASURES--Concentration of plasma luteinizing hormone (LH), oestradiol (E2) and progesterone, number of ovulatory follicles induced and the occurrence of pregnancy. RESULTS--Plasma LH, E2 and progesterone concentrations were reduced in the late follicular phase after buserelin/hMG compared with CC/hMG. Buserelin/hMG promoted the development of more follicles than CC/hMG. The overall pregnancy rate after buserelin/hMG was not significantly different from that following CC/hMG treatment. CONCLUSION--The chance of pregnancy is not improved by the short-term use of buserelin with hMG, provided adequate follicular phase management is maintained.