Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study

BACKGROUND: Patients with polycystic ovary syndrome (PCOS) may need a longer period of pituitary downregulation to suppress the elevated serum LH and androgen levels effectively during IVF treatment using the GnRH agonist long protocol. We proposed a stimulation protocol incorporating Diane-35 and GnRH antagonist (Diane/cetrorelix protocol) and compared it with the GnRH agonist long protocol for PCOS patients. METHODS: Part I of the study was an observational pilot study to evaluate the hormonal change as a result of the Diane/cetrorelix protocol (n = 26). Part II of the study was a prospective randomized study comparing the Diane/cetrorelix protocol (n = 25) and the GnRH agonist long protocol (n = 24). In the Diane/cetrorelix protocol, patients were pre-treated with three cycles of Diane-35, followed by 0.25 mg of cetrorelix on cycle day 3. From day 4, cetrorelix and gonadotrophin were administered concomitantly until the day of HCG injection. RESULTS: Serum LH, estradiol and testosterone levels were suppressed comparably in both protocols at the start of gonadotrophin administration. Serum LH was suppressed at constant levels without a premature LH surge in the Diane/cetrorelix protocol. The clinical results for both protocols were comparable, with significantly fewer days of injection, lower amounts of gonadotrophin used and lower estradiol levels on the day of HCG injection following the Diane/cetrorelix protocol. Furthermore, there was no significant difference in clinical pregnancy outcome between the two stimulation protocols. CONCLUSIONS: The Diane/cetrorelix protocol has a similar pregnancy outcome to the GnRH agonist long protocol for women with PCOS undergoing IVF treatment.     

Endocrinology: Human chorionic gonadotrophin self-administered by the subcutaneous route to induce oocyte maturation in an in-vitro fertilization and embryo transfer programme

This study was initiated to evaluate oocyte maturation and theoutcome of in-vitro fertilization (IVF) cycles following thes.c. administration of human chorionic gonadotrophin (HCG) bythe patient herself or her partner. A group of 104 women whoentered our IVF embryo transfer programme were prospectivelyrandomized to have 5000 IU or 10 000 IU HCG s.c. or i.m. TheHCG was administered for induction of the final oocyte maturationin cycles with pituitary down-regulation with a gonadotrophin-releasinghormone agonist according to a long protocol and where ovarianstimulation had been achieved with pure follicle stimulatinghormone. The mean concentration of HCG in serum 12 and 36 hafter the HCG injection was significantly higher in the womenreceiving 5000 IU i.m. compared to the s.c. route. However,in women receiving 10 000 IU HCG there were no significant differencesin the mean concentrations 12 and 36 h after the injection,irrespective of the route of administration. Furthermore, therewere no significant differences in the relative numbers of retrievedmature oocytes between the groups. When comparing the clinicaloutcome in the different groups, no significant differenceswere found between those receiving 5000 IU or 10 000 IU HCG,i.m. or s.c. Our data indicate that HCG can be given s.c. withoutreducing the chance of retrieving a mature oocyte and that theclinical outcome with regard to pregnancies is not negativelyaffected.     

Continuous administration of gonadotrophin-releasing hormone agonist during the luteal phase in IVF

BACKGROUND: It has been reported that ceasing the administration of gonadotrophin-releasing hormone (GnRH) agonist causes a profound suppression of circulating serum gonadotrophins. A comparative prospective and randomized study was conducted to investigate the effect of continuous administration of GnRH agonist during the luteal phase in an ovarian stimulation programme for IVF. METHODS: GnRH agonist was administered intranasally from the midluteal phase of the previous cycle, and pure FSH administration started on cycle day 7. In the continuous-long protocol (cL) group (n = 161 ), GnRH agonist administration was continued until 14 days after oocyte retrieval. In the long protocol (L) group (n = 158 ), GnRH agonist was administered until the day before human chorionic gonadotrophin (HCG) administration. RESULTS: The implantation rate and live birth rate per unit of transferred embryos were significantly higher in the cL group than the L group (P < 0.05 ). Serum LH and FSH concentrations on the day of, and 1 day after, HCG administration were significantly lower in the L group than the cL group (P < 0.01 ). CONCLUSIONS: Continuation of GnRH agonist administration during the luteal phase might facilitate implantation, and prevent the profound suppression of serum gonadotrophins.     

Programming of ovarian stimulation with norethindrone acetate in IVF/GIFT cycles

Twenty patients were given norethindrone acetate (NET) to program the initiation of controlled ovarian hyperstimulation and to coordinate follicular aspiration with surgery to obtain spermatozoa from the husband. Patients received NET, 10 mg/day orally, starting between days 2 and 4 of the cycle. The duration of NET therapy varied from 9 to 37 days. The mean time of onset of vaginal bleeding, after cessation of NET, was 2.9 +/- 0.7 days. Ovarian stimulation was carried out with a combination of a luteinizing hormone releasing hormone analog, follicle-stimulating hormone and human menopausal gonadotrophin. The day of human chorionic gonadotrophin (HCG) administration ranged from day 8 to day 15 of the cycle (10.1 +/- 1.7). On the day of HCG injection, the mean E2 level was 2188 +/- 1126. The mean number of follicles aspirated was 18.4 +/- 9.9 per cycle. The mean number of oocytes collected per cycle was 15.5 +/- 8.5. There was no correlation between duration of NET suppression and the number of days of gonadotrophin therapy needed to reach HCG administration. The large number of oocytes retrieved is probably related more with the fact that the patients represented a group with a purely male factor of infertility, than by the specific drug protocol utilized. Our results demonstrate that the ovarian response to gonadotrophin stimulation was not affected by NET administration. The main advantages of the use of this drug for cycle control are that its administration is oral, simple and inexpensive.     

Analysis of the bleeding pattern in assisted reproduction cycles with luteal phase supplementation using vaginal micronized progesterone

This study was designed to determine the effects of a vaginal micronized progesterone preparation on bleeding patterns and pregnancy outcomes after in-vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). The study population consisted of 149 consecutive women who had undergone IVF-ICSI using 'long-protocol' stimulation with buserelin-human menopausal gonadotrophin (HMG). A retrospective chart analysis of computerized medical records was undertaken. Vaginal progesterone (200 mg three times daily) was begun the day before oocyte retrieval and continued for a minimum of 16-19 days following human chorionic gonadotrophin (HCG) administration. Occurrence of bleeding following HCG injection, pregnancy rate and outcomes, and serum concentrations of oestradiol were measured. Women undergoing IVF and embryo transfer with ICSI and using vaginal progesterone for luteal support had normal luteal phase lengths (day of HCG minus day of onset of bleeding). In the absence of pregnancy, bleeding occurred after 19.2 +/- 3.9 days (mean +/- SD). Out of the pregnant group only three women bled within 19 days of HCG administration: two had biochemical pregnancies which spontaneously vanished and one evolved to term. The results reflect the normal bleeding pattern to be expected when vaginal progesterone is used for luteal support in IVF and embryo transfer, an approach whose efficacy has been amply proven. No shortened luteal phases were observed using vaginally administered progesterone.     

三种方法治疗未破裂卵泡黄素化综合征的疗效分析

目的 比较3种方法治疗未破裂卵泡黄素化综合征（LUFS）疗效。方法 将34个病例56个治疗周期随机分成3个治疗组：A组（HCG组），B组（单次GnRH—a组），C组（GnRH—a＋HCG组），观察3组患者的妊娠率，排卵率，并分别于HCG／达必佳注射日及排卵后7日抽取外周血测LH，P，观察各组有无差异。结果 3种治疗方法的排卵率有统计学差异（P〈0．05），C组的排卵率显著高于B组，A组。而3组的妊娠率则无明显差异（P〉0．05）。HCG／达必佳注射日3组血LH有统计学差异（P〈0．05），C组低于A组与B组，而血P值则3组之间无统计学差异（P〉0．05）。排卵后7日血P值3组之间亦有统计学差异（P〈0．05），A组高于C组，C组高于B组。结论 GnRH—a＋HMG方案能有效的降低HCG注射日LH值。提高LUFS患者的排卵率，但妊娠率无明显改善。     

Rescue of IVF cycles by HMG in pituitary down-regulated normogonadotrophic young women characterized by a poor initial response to recombinant FSH

BACKGROUND: The aim of this study was to investigate the effects of adding human menopausal gonadotrophin (HMG) during controlled ovarian stimulation in normoovulatory normogonadotrophic patients showing an initial suboptimal response to a standardized long protocol therapy with recombinant FSH (rFSH) (300 IU/day). METHODS: A total of 43 such patients were randomized in two groups. In Group A, 150 IU rFSH was substituted by 150 IU HMG after day 8 of stimulation. The stimulation protocol of Group B involved a simple increase of the daily rFSH dose to 375 IU after day 8. A total of 40 BMI and age matched patients with an optimal ovarian response formed the control group (Group C). RESULTS: The mean Group A serum concentration of oestradiol on the day of HCG administration and average number of oocytes retrieved were significantly higher than Group B (P < 0.001) and equivalent to Group C. A total of 10 pregnancies (50%) in Group A, 8 (34.8%) in Group B and 19 (47.5%) in the control group were achieved. CONCLUSIONS: The data suggest that LH supplementation improves the ovarian outcome in patients characterized by an inadequate initial response to rFSH therapy in a long protocol.     

Combination of long and short term GnRH analogue protocols: a new therapeutic approach to persistent high progesterone levels in IVF cycles.

Thirty-four patients who had had persistently high progesterone (P) levels during menotrophin therapy in previous in-vitro fertilization (IVF) cycles, despite pretreatment with a long acting gonadotrophin-releasing hormone analogue (GnRHa), were randomly divided into two groups according to the mode of ovulation induction used. In 16 women (group 1), induction of ovulation was performed with decapeptyl (DTRP6)/pure follicle-stimulating hormone (PFSH)/human menopausal gonadotrophin (HMG)/human chorionic gonadotrophin (HCG). In 18 patients (group II), the protocol was identical to the former group, except for the addition of a short-acting GnRHa (buserelin) that was started when P levels were persistently high. The combination of long and short acting GnRH analogues (group II) resulted in an improved follicular phase with significantly lower P levels on the day of HCG administration (P less than 0.001). Furthermore, a significantly higher number of oocytes was retrieved, fertilized and cleaved (P less than 0.005; P less than 0.001; P less than 0.005, respectively) and, as a consequence, significantly higher pregnancy rates were achieved (22.2 versus 12.5%; P less than 0.005). These results indicate that a combination of long- and short-acting GnRH agonists may be of value in cases of persistent high P levels during menotrophin therapy in IVF cycles. Further larger studies must be performed before the true efficacy of this mode of treatment can be determined.     

Premature luteinization is not eliminated by pituitary desensitization with leuprolide acetate in women undergoing gonadotrophin stimulation who demonstrated premature luteinization in a prior gonadotrophin-only cycle

A total of 40 women who demonstrated premature luteinization(serum progesterone 3.5 nmol/1 (1.1 ng/ml) on or before theday of human chorionic gonadotrophin (HCG) administration) duringovarian stimulation with human menopausal gonadotrophins (HMG)were restimulated in 46 subsequent cycles after pituitary desensitizationwith the gonadotrophin-releasing hormone agonist (GnRHa, 1 mg),leuprolide acetate. Five women were treated with a double doseof agonist (2 mg) when premature luteinization was determinedon the single dose protocol. In HMG-only cycles, a frank luteinizinghormone (LH) surge was detected in 30 cycles; 15 cycles werecancelled because of premature ovulation. In agonist cyclesthere were no cancellations, although 25 cycles demonstratedpremature luteinization and in six cycles a frank LH surge wasdetected. Doubling the dose of the agonist did not prevent prematureluteinization. Agonist cycles with and without premature luteinizationdid not differ in any in-vitro fertilization (IVF) outcome parameters(ampoules of gonadotrophins, day of HCG administration, peakoestradiol concentration, number of oocytes retrieved, fertilized,transferred or cryopreserved). We conclude that in patientswho demonstrate premature luteinization in a gonadotrophin-onlycycle, pituitary desensitization may not completely eliminatesubtle luteinization or a frank LH surge.     

Intrauterine insemination: effect of the temporal relationship between the luteinizing hormone surge, human chorionic gonadotrophin administration and insemination on pregnancy rates

The optimal time period for intrauterine insemination (IUI) in relation to either luteinizing hormone (LH) surge or human chorionic gonadotrophin (HCG) administration leading to the best pregnancy rates has not been determined. In this study, 856 consecutive human menopausal gonadotrophin (HMG)-stimulated and 49 natural unstimulated IUI cycles carried out at a reproductive medicine unit affiliated with a tertiary centre were analysed in a retrospective fashion. There were three scenarios in the temporal relationship of the LH surge, HCG administration and artificial insemination. These were (group A) subjects who had an endogenous LH surge but were not given HCG; (group B) subjects who were given HCG after an observed LH surge, and (group C) subjects who were given HCG before the LH surge. The overall pregnancy rate (PR) was 16% per cycle. The PR was 9% in group A, 20% in group B and 14% in group C. The PR in group B was significantly better than group C (P = 0.04). In group B, the longer the time interval between the LH surge and HCG administration, the better the PR up to 20 h (P = 0.025); the timing of IUI based on the LH surge was not critical to the achievement of pregnancy within 3 days. In group C, PR improved with the increasing interval between HCG and IUI from <28 h up to 60 h. We conclude that a better PR is achieved if a spontaneous LH surge occurs before HCG administration, especially where the administration of HCG is delayed 8-20 h after an observed LH surge; the timing of IUI based on the LH surge is not critical to the achievement of pregnancy within 3 days.      

Influence of the duration of the oestradiol rise on the success rate in GnRH analogue/HMG-stimulated IVF cycles

The influence of the duration of the serum oestradiol (E2) rise before human chorionic gonadotrophin (HCG) injection on the outcome of in-vitro fertilization (IVF) cycles was investigated. Two different stimulation protocols were compared. In 218 cycles, the Norfolk protocol for stimulation with human menopausal gonadotrophin (HMG) was used (protocol A). In 235 cycles, pituitary function was suppressed by a single injection of a long-acting GnRH analogue ('Decapeptyl microcapsules') before HMG stimulation was started (protocol B). The overall pregnancy rates were significantly higher with protocol B (22% per puncture, 21% per started cycle) than with protocol A (14% per puncture, 9% per started cycle). For each interval of E2 rise duration (5-11 days), the fertilization rates (per oocyte) and the pregnancy rates (per puncture) were evaluated. There was a clear-cut maximum of the pregnancy rates for 6 and 7 days of E2 rise (21 and 16% respectively) for protocol A. For protocol B, pregnancy rates were generally higher than for protocol A. There was also a maximum of the pregnancy rates for 6 (32%) and 7 (29%) days of E2 rise but this maximum was not as clear-cut as for protocol A. The fertilization rates showed no significant differences for each interval of E2 rise in both groups (between 63 and 89%). Therefore, it is concluded that endometrial maturity, and not the oocyte's ability for fertilization, is the most critical factor for success in IVF cycles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pituitary gonadotrophin secretory capacity during the luteal phase in superovulation using GnRH-agonists and HMG in a desensitization or flare-up protocol.

Pituitary gonadotrophin reserve and basal gonadotrophin secretion were tested during the luteal phase in women superovulated with buserelin/human menopausal gonadotrophin (HMG) in a desensitization (n = 17) or flare-up protocol (n = 7). In the desensitization protocol the luteinizing hormone-releasing hormone (LHRH) stimulated serum LH and follicle stimulating hormone (FSH) concentrations remained impaired at least until day 14 after arrest of the agonist. In the flare-up protocol basal and stimulated LH secretion was still abnormal on days 14 and 15 after human chorionic gonadotrophin (HCG) injection. Normal basal serum FSH concentrations were measured at the end of the luteal phase in the flare-up protocol, but the response of FSH to LHRH injection was still subnormal. We conclude that gonadotrophin function remained impaired until the end of the luteal phase after desensitization and flare-up GnRH-agonist and HMG stimulation protocols. Corpus luteum stimulation with exogenous HCG or substitution therapy using natural progesterone are required to prevent the possible negative effects resulting from pituitary dysfunction after GnRH-agonist treatment.     

Infertility: Intra-uterine insemination or timed intercourse after ovarian stimulation for male subfertility? A controlled study

In this randomized trial we investigated whether intra-uterineinsemination (IUI) in couples with male subfertility leads toa higher probability of conception than timed intercourse afterovarian stimulation with human menopausal gonadotrophin (HMG)and human chorionic gonadotrophin (HCG). A total of 76 couplesstarted 249 cycles, of which 47 were cancelled to prevent multiplepregnancies or hyperstimulation. After 202 completed treatmentcycles, 15 pregnancies occurred, 11 after IUI and four aftertimed intercourse. The pregnancy rate per completed cycle withIUI was 10.3% (95% confidence interval: 5.5–17.5%) and4.2% (1.2–10.1%) with timed intercourse. Compared withthe estimated spontaneous chance to conceive, IUI after ovarianstimulation appeared to be more effective in the first threecycles. We conclude that in subfertile couples with a male factor,IUI tends to improve the probability of conception as comparedto timed intercourse when ovarian stimulation is applied, andwe advise such treatment for three cycles.     

Assessment of serum luteinizing hormone during ovarian stimulation with gonadortrophins

An immunoradiometrte assay (IRMA), using monoclonal antibodieswith high affinity for human luteinizing hormone (HLH), wasevaluated for quantitative measurement of serum LH after humanchorionic gonadotrophin (HCG) administration in patients undergoingstimulation of multiple folh'cular development. Compared toa radioimmunoassay (RIA) commonly used to monitor serum LH,LH IRMA was more effective by several orders of magnitude indiscriminating between HLH and HCG and showed no crossreactivityat HCG concentrations normally found in serum after hormonetreatment. Assays of serum samples obtained from 10 patientsreceiving HCG as part of an HMG/HCG protocol to induce ovulationfor IVF/GIFT also demonstrated that RIA values were greatlyaffected by exogenous HCG. It was estimated that 17–32%of serum HCG was measured as serum LH in RIA. In contrast, determinationsof serum LH by IRMA was not biased by exogenous HCG. Data fromIRMA indicated that eight of the 10 patients showed a significantrise in LH secretion, relative to mean baselines, at either12 or 36 h after adminstration. In one patient the rise hadalready occurred before HCG administration. When an LH riseoccurred, either before or after HCG injection, mean valueswere 2to 9fold higher than those of baseline levels. Assumingthat LH rises > 12 mlU/ml may relate to an endogenous surgeof LH, none of the patients showed a surge prior to HCG administration.On the contrary, the occurrence of an ‘LH surge’after HCG was apparent in four patients. These data demonstratethe application of monoclonal antibodies incorporated in anIRMA to study the occurrence of endogenous LH surges duringstimulation of follicular development by gonadotrophins.     

Treatment of hyperstimulation during in-vitro fertilization

In 33 patients treated with a combination of an LHRH agonist (LHRH-A) and gonadotrophin in a long protocol, a biological hyperstimulation occurred (E2 greater than 2500 pg/ml on the day of HCG administration and 4722 +/- 1190 pg/ml the day after, with greater than 10 follicles greater than 12 mm on each ovary). The replacement of fresh embryos were deferred and LHRH-A was continued, and an endometrial biopsy was performed on the theoretical day of replacement (2 days after oocyte recovery). With this technique, we obtained a mean number of 17.9 +/- 7 oocytes, a fertilization rate of 49% and a replacement rate of 87% in a deferred cycles. The overall pregnancy rate of frozen-thawed embryos was 27% in the seven spontaneous cycles, 12 induced cycles and 10 artificial cycles. Only one severe hyperstimulation occurred and this case emphasizes that caution remains necessary even with this technique.     

Endocrinology: A comparison between a standard and reduced dose of D-Trp-6-luteinizing hormone-releasing hormone administered after pituitary suppression for in-vitro fertilization

A randomized prospective study was undertaken to compare lowand standard luteinizing hormone-releasing hormone agonist (LHRHa)dosage used in combination with gonadotrophins in ovarian stimulationfor in-vitro fertilization (IVF). A total of 42 ovulatory patientswith mechanical infertility were administered 0.5 mg/day LHRHa(Decapeptyl) from day 21 of their cycles for 14 days. Followingdown-regulation, patients were randomly allocated to continuewith the same dose of LHRHa (22 patients, group A) or to receivea lower dose of 0.1 mg/day LHRHa (20 patients, group B) duringfolliculogenesis. Luteal phase was supported by daily i.m. progesterone(50 mg) injections and human chorionic gonadotrophin (HCG; 1500IU) every 4 days. Ovarian response, human menopausal gonadotrophin(HMG) dosage used for induction of ovulation, evidence of prematureluteinization, and clinical and laboratory IVF outcome, werecompared between groups A and B. The two groups were comparablein respect of: age (32.6 ± 0.7 and 33.0 ± 0.9years), HMG dosage (33.0 ± 1.6 and 36.0 ± 2.5ampoules), day of HCG (11.2 ± 0.3 and 12.2 ± 0.4),oocytes/patient (13.3 ± 1.0 and 12.9± 1.3), fertilizationrate (68.5 and 65.2%), cleavage rate (95% for both), pregnancy/embryotransfer (32 and 35%) and implantation rate (10.8 and 10.5%),for groups A and B respectively. There was no evidence of prematureluteinization or luteolysis in either group. It was concludedthat lowering the dose of LHRHa to 0.1 mg/day during folliculogenesishad no adverse effect on ovarian response or clinical results.However, it had no advantage in reducing the HMG dose used forovulation induction.     

Clinical outcome with half-dose depot triptorelin is the same as reduced-dose daily buserelin in a long protocol of controlled ovarian stimulation for ICSI/embryo transfer: a randomized double-blind clinical trial (NCT00461916)

BACKGROUND: Traditional doses of depot GnRH agonist may be excessive for ovarian stimulation. We compared half-dose depot triptorelin (Group I) with reduced-dose daily buserelin (Group II) in a long protocol ICSI/embryo transfer through a double-blind randomized clinical trial. METHODS: Controlled ovarian stimulation (COS) was started by a pretreatment with oral contraceptives for 21 days. Then, 182 patients were randomized into two groups of 91. Group I received 1.87 mg triptorelin depot i.m. followed by daily s.c. injections of saline. Group II (reduced-dose protocol) received a bolus injection of i.m. saline followed by daily s.c. injections of 0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotrophin stimulation. When transvaginal ultrasound showed at least two follicles of 16-20 mm diameter, HCG was given and ICSI was performed 40-42 h later. RESULTS: No significant differences were seen in the mean (SD) number of follicles at HCG administration, as our primary outcome [10.3 (4.4) in Group I versus 11.1 (4.2) in Group II, P = 0.180, mean difference = 0.86, 95% confidence interval 0.39-2.11]. The other early results of COS, clinical and ongoing pregnancy rates, or early pregnancy loss were also not significantly different between the groups. Group I endured longer stimulation period [11.2 (1.8) days versus 10.6 (1.9), P = 0.030]. CONCLUSIONS: Clinical outcomes were not significantly different between Group I and Group II.     

Preliminary experience of the use of a gonadotrophin-releasing hormone antagonist in ovulation induction/in-vitro fertilization prior to cancer treatment.

Therapeutic regimens for the treatment of malignant disease may compromise future fertility. One approach to circumvent this is the cryopreservation of embryos created before treatment for the malignancy. Conventional regimens using gonadotrophin-releasing hormone (GnRH) agonists are time consuming, requiring pituitary down-regulation before gonadotrophin administration, thus the duration of treatment is approximately 20-30 days. GnRH antagonists, however, do not cause an initial stimulation of gonadotrophin secretion and can thus be administered during the later stages of follicular maturation to prevent premature luteinization and ovulation. The duration of ovulation induction/in-vitro fertilization (IVF) treatment is thus reduced. In this study, case histories are reported of six women with newly diagnosed malignancies who requested ovulation induction/IVF prior to chemotherapy or surgery in which we have used the GnRH antagonist Cetrorelix. Gonadotrophin administration was started in the early follicular phase, and Cetrorelix (0.25 mg s.c. daily) was added from day 6 of treatment. Subsequent to human chorionic gonadotrophin (HCG) administration oocytes were recovered and successful fertilization and embryo cryopreservation was achieved in all cases. The median duration of treatment was 12 days (range 8-13, including induction of luteolysis in two patients). These results illustrate the potential use and advantages of a GnRH antagonist in ovulation induction/IVF when the need for immediate initiation of treatment and its duration are critical factors.     

Complete and partial luteinized unruptured follicle syndrome after ovarian stimulation with clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin

A total of 31 clomiphene citrate/human menopausal gonadotrophin(HMG)/human chorionic gonadotrophin (HCG)-stimulated cyclesin 28 patients were investigated to determine the fate of eachof the matured follicles. A standard stimulation regimen wasadhered to, and ultrasound as well as hormonal monitoring wasperformed. All follicles were measured by vaginal ultrasoundat –12, +35 and +45 h relative to HCG administration andat 7 days after HCG administration. Of the 220 follicles, 107(48.6%) ruptured. The number of ruptured follicles per cyclewas correlated with the mid-luteal progesterone concentration(r = 0.63, P = 0.0005). The probability of follicular rupturewas related to follicular diameter at 12 h before HCG administration;6% of follicles <12 mm in diameter ruptured compared with87% of follicles 18–19 mm. A complete luteinized unrupturedfollicle (LUF) syndrome was observed in six cycles (20%). Inthese cycles, follicular growth and oestradiol, progesterone,luteinizing hormone (LH) and follicle stimulating hormone (FSH)concentrations at 12 h before HCG administration were similarto those in cycles with follicular rupture. However, mid-lutealprogesterone concentrations were lower in complete LUF cycles(46.97 ± 8.95 nmol/1 versus 108.74 ± 12.27 nmol/1;P = 0.02). These data demonstrate that in stimulated cyclesmany follicles, usually the smaller ones, fail to rupture, evenafter HCG administration. Complete LUF syndrome, despite a strongexogenous ovulatory signal, and the absence of any differencein peri-ovulatory hormonal parameters, indicates that the defectcausing LUF resides in the follicle itself and/or hormonal changesduring the follicular phase.     

Transfers of frozen-thawed human embryos in cycles stimulated by HMG

A total of 130 transfers of frozen-thawed (F-T) human embryos was carried out after moderate ovarian stimulation with human menopausal gonadotrophin (HMG). Embryos were replaced 3 days after the spontaneous luteinizing hormone (LH) surge or 4 days if ovulation was induced by human chorionic gonadotrophin (HCG). Embryos were thawed a few hours prior to transfer. One-hundred-and-twenty-three transfers were effective and 23 pregnancies were achieved. The rate of ongoing pregnancies per transfer was 17.9% (22/123). The survival rate of embryos originating from cycles stimulated by a combination of an LHRH analogue and HMG in a long protocol (LA-HMG protocol) was significantly lower when compared with the rate of embryos retrieved from clomiphene citrate-HMG (CC-HMG protocol) stimulated cycles (52 versus 67%, P less than 0.05). When fresh embryos originated from cycles stimulated with an LHRH analogue and HMG in a short protocol (SA-HMG protocol), the survival rate was not affected (59 versus 67%, NS). Although the difference was not significant, the ongoing pregnancy rate per transfer according to the three protocols from which the embryos originated seemed to be better with the SA-HMG protocol: 16% with the CC-HMG protocol, 14.5% with the LA-HMG protocol versus 27.6% with the SA-HMG protocol. The success rate was independent of the number of F-T transferred embryos if at least one embryo with 100% intact blastomeres was replaced.