Spontaneous luteinizing hormone surges can be reliably prevented by the timely administration of a gonadotrophin releasing hormone antagonist (Nal-Glu) during the late follicular phase.

A new gonadotrophin releasing hormone antagonist (Nal-Glu) was used during the late follicular phase of the natural cycle in order to prevent spontaneous surges of luteinizing hormone (LH). Eight regularly ovulating women (group 1) received two injections of Nal-Glu (5 mg) administered 48 h apart when plasma oestradiol levels exceeded 125 pg/ml. Human menopausal gonadotrophin (HMG, 225 IU) was administered simultaneously with Nal-Glu and repeated every 12 h thereafter until either a spontaneous LH surge occurred or human chorionic gonadotrophin (HCG, 5000 IU) was administered. HCG was arbitrarily administered 48 h after the second Nal-Glu injection. Six other women (group 2) receiving only HMG served as controls. In seven of the eight women in group 1, LH and progesterone remained low for 96 h following Nal-Glu, i.e. until HCG administration. In the remaining woman in this group, LH started to rise 12 h before HCG injection. In this group, Nal-Glu did not interfere with follicular development or the plasma profile of oestradiol. All women developed one single dominant follicle with the exception of one subject who had already spontaneously developed two dominant follicles prior to administration of Nal-Glu and HMG. In group 2, LH rose spontaneously in all women before the planned HCG injection. The luteal phase was apparently not altered by Nal-Glu. These results suggest that Nal-Glu administration during the late follicular phase of natural cycles supported by HMG, can prevent the spontaneous LH surge while not interfering with follicular growth.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. European Cetrorelix Study Group

In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.     

Premature luteinization of follicles during ovarian stimulation for in-vitro fertilization

The structure and growth of developing follicles was monitored using vaginal ultrasound scanning in an outpatient programme of in-vitro fertilization (IVF) and embryo transfer (ET). Patients received either human menopausal gonadotrophin (HMG) alone or clomiphene citrate (CC) + HMG for controlled ovarian stimulation. Ultrasound data were compared with pre-ovulatory oestradiol (E2), luteinizing hormone (LH) and progesterone (P) levels. Hormonal parameters and results were classified according to the main indications of IVF-ET treatment. Twenty-one of the 271 patients in the study showed ultrasonic evidence of premature luteinization (PL) of follicles, thickening of the follicular wall and the appearance of irregular echogenic structures in the follicle. PL was preceded in eight cases by an indisputable LH surge and subsequent P elevation. In the remaining 13 cases PL occurred either due to an abortive LH surge not exceeding by 3-fold the baseline values or as a result of HMG administration. Special attention was paid to the P pattern prior to and after human chorionic gonadotrophin (HCG) administration. PL cycles demonstrated significantly (P less than 0.05) higher P levels before HCG administration and at the time of oocyte retrieval as well. Because implantation was not achieved in these cases, the cancellation of PL cycles is recommended. Vaginal ultrasound scanning seems to be helpful in the evaluation of minor changes in the follicular structure, correlating frequently with hormonal findings.     

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.     

Comparison of the effects of HMG or pure FSH stimulation during suppression with an LHRH agonist analogue.

Infertile patients who responded poorly in an in-vitro fertilization programme were treated with human menopausal gonadotrophin (HMG) or with pure follicle stimulating hormone (FSH) during continuous administration of a luteinizing hormone-releasing hormone (LHRH) agonist, to determine whether a low level of LH is required for follicle maturation. No statistically significant differences were detected in the dose of gonadotrophins, duration of treatment, oestradiol and LH levels, numbers of recovered oocytes, transferred embryos or fertilization rates. It is concluded that an absence of low levels of LH does not disturb follicular development in the follicular phase. Based on the low fertilization rates in the present study (0.32 with HMG versus 0.45 with FSH) the authors suggest that, as well as hormonal deficiency, other factors may also influence follicular and early embryonic development.     

Blunted LH surge after HCG administration in cycles superovulated for in-vitro fertilization

The preovulatory pattern of serum luteinizing hormone (LH) was investigated in cycles superovulated for in-vitro fertilization (IVF). The method used was immunoradiometric assay which shows no cross-reactivity with human chorionic gonadotrophin (HCG) at concentrations usually found after HCG administration. Of the 245 cycles stimulated by clomiphene citrate + human menopausal gonadotrophin, an endogenous LH surge was observed in 29.8% of the patients shortly prior to the HCG injection. In the post-HCG period, 49.4% of the cycles exhibited a blunted LH rise, whereas in the remaining 20.8% the LH level did not exceed twice the mean preovulatory value. According to the oestradiol-17 beta (E2) and progesterone concentrations, different hormonal patterns were found in patients with pre-HCG and post-HCG elevation of LH. However, the occurrence of a blunted LH surge following HCG administration cannot be attributed to different, HCG-induced secretory patterns of progesterone. There were no significant differences in clinical parameters, the pregnancy rate was slightly but not significantly higher (19.0%) in the post-HCG LH surge group than in the two other groups (13.7%). It is presumed that various factors may contribute to the suspension of preovulatory LH suppression. The possible beneficial influence of a post-HCG surge of LH requires further investigation.     

The effect of progesterone supplementation prior to the induction of ovulation in women treated for in-vitro fertilization

Thirty-one patients superovulated with clomiphene citrate (CC)and human menopausal gonadotrophin (HMG) were given a singleinjection of 25 mg progesterone (P group) 6 h prior to injectionof human chorionic gonadotrophin (HCG). Levels of urinary andplasma luteinizing hormone (LH) were significantly higher (P<0.001)immediately prior to HCG in the P group compared with thirty-onecontrol patients who had HCG on the same night. Plasma levelsof progesterone remained significantly elevated (P<0.02)for 80 h after injection in the P group, thereafter the levelwas similar to controls. The number of oocytes recovered, fertilizedand replaced per patient was identical in both groups. However,four control patients had no embryos replaced due to failedfertilization. It is concluded that (i) in the majority of Ppatients the timing of ovulation induction by HCG injectionwas appropriate as an LH surge was elicited thus reflectinga physiological stage of readiness, and (ii) elevated plasmaprogesterone levels around the time of oocyte recovery and inthe early luteal phase do not increase the likelihood of theestablishment of pregnancy in patients stimulated for in-vitrofertilization and embryo replacement (TVF/ER) with CC and HMG.     

Premature luteinization: treatment and incidence in natural cycles

The incidence of premature luteinization was evaluated in 400 women with a history of infertility (greater than or equal to 18 months). After its diagnosis, this condition was treated with ovulation-inducing drugs in the early follicular phase in an attempt to accelerate follicular maturation before the luteinizing hormone (LH) surge. Premature luteinization was diagnosed if serum progesterone levels greater than 1.5 ng/ml were associated with an LH surge before the serum oestradiol level reached 200 pg/ml and before the follicle was mature. Fifty-two of 400 (13%) women demonstrated premature luteinization in two consecutive cycles. Fourteen of 52 (27%) women corrected the problem with a clomiphene citrate regimen, as compared with 32 of 38 (75%) treated with HMG and HCG; conception rates were 83 and 50%, respectively, for the patients who responded to the two regimens. Overall, regimens utilized in this study resulted in a 58% pregnancy rate in 6 months.     

Differential effects of gonadotrophin-releasing hormone agonists administered as desensitizing or flare protocols on hormonal function in the luteal phase of hyperstimulated cycles

The incorporation of gonadotrophin-releasing hormone agonist (GnRHa) in in-vitro fertilization (IVF) stimulation protocols has led to doubt about the quality of the subsequent luteal phase. The effects of two GnRHa stimulation protocols on luteal phase concentrations of oestradiol (E2), progesterone (P), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were compared with the standard clomiphene stimulation regimen. Subjects receiving clomiphene with human menopausal gonadotrophin (HMG, n = 377) showed essentially similar luteal phase P concentrations to those receiving leuprolide acetate/HMG as a desensitization protocol. Subjects receiving concomitant leuprolide and HMG from day 2 to utilize the flare effect of the GnRHa exhibited significantly lower P levels in the luteal phase compared to clomiphene/HMG and leuprolide desensitization protocols despite the addition of HCG support. This occurred despite equivalent E2 concentrations at the time of ovulation and identical numbers of oocytes recovered. LH concentrations in non-conception cycles were suppressed for at least 14 days in the luteal phase in both GnRHa protocols compared to clomiphene stimulation. Differences were less obvious in cycles where conception occurred suggesting that implantation may proceed more favourably when the luteal endocrinology was optimal. It is concluded that flare methods of GnRHa hyperstimulation are associated with significantly different luteal phases compared with clomiphene or desensitization protocols. It is proposed that the use of the flare type of stimulation may significantly influence the response of the granulosa cells to LH or HCG via gonadotrophin receptors or through altered post-receptor function.     

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.      

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.     

Comparison of LH concentrations in the early and mid-luteal phase in IVF cycles after treatment with HMG alone or in association with the GnRH antagonist Cetrorelix

Luteinizing hormone (LH) is mandatory for the maintenance of the corpus luteum. Ovarian stimulation for IVF has been associated with a defective luteal phase. The luteal phases of two groups of patients with normal menstrual cycles and no endocrinological cause of infertility were retrospectively analysed in IVF cycles. Thirty-one infertile patients stimulated with human menopausal gonadotrophins (HMG) for IVF to whom the gonadotrophin-releasing hormone (GnRH) antagonist Cetrorelix 0.25 mg was also administered to prevent the LH surge (group I) were compared with 31 infertile patients stimulated with HMG alone (group II). Despite differences in the stimulation outcome, luteal LH serum concentrations were similar in the two groups. LH values dropped from 2.3 +/- 1 IU/l on the day of human chorionic gonadotrophin (HCG) administration to 1.1 +/- 0.7 IU/l on day HCG +2 in group I (P < 0.0001) and from 5.1 +/- 3 to 1.2 +/- 1.7 IU/l (P < 0.0001) in group II. In the mid-luteal phase, LH concentrations were low in both groups. Our results suggest that suppressed LH concentrations in the early and mid-luteal phase may not be attributed solely to the GnRH-antagonist administration. Pituitary LH secretion may be inhibited by supraphysiological steroid serum concentrations via long-loop feedback and/or by the central action of the exogenously administered HCG via a short-loop mechanism.     

Subcutaneous low dose leuprolide acetate depot versus leuprolide acetate for women undergoing ovarian stimulation for in-vitro fertilization

A total of 100 women undergoing ovarian stimulation with gonadotrophin-releasinghormone agonist (GnRHa) and a human menopausal gonadotrophin(HMG) for in-vitro fertilization (IVF) participated in thisrandomized comparative study. Leuprolide acetate at a dose of0.5 mg/day s.c. (n = 52, group I), or low-dose leuprolide acetatedepot at a dose of 1.88 nig s.c. (n = 48, group II), was startedon days 21–23 of the cycle. Stimulation with 225 IU/dayHMG was started after pituitary desensitization had been achieved.The luteal phase was supported by human chorionic gonadotrophin(HCG) i.m. injection. There were nostatistical differences inbaseline oestradiol (24.5 ± 4.8 versus 21.9 ±4.5 pg/ml) and follicle stimulating hormone (FSH) concentrations(3.9 ± 1.9 versus 3.2 $ 1.8 mlU/ml), and concentrationson the day of HCG administration of oestradiol (1657 ±245 versus 1512$165 pg/ml), luteinizing hormone (LH; 6.2 ±4.8 versus 5.6 ± 4.3 mlU/ml) and FSH (10.6 ± 2.8versus 10.8 ± 3.6 mIU/ml). There were also no statisticaldifferences in the HMG dosage (26.8 ± 1.8 versus 28.5± 1.5), the number of oocytes retrieved (7.6 ±3.0 versus 8.1 ± 4.3), the number of oocytes fertilized(5.3 ± 2.1 versus 5.6 ± 3.0) and the number ofembryos transferred (3.5 ± 1.3 versus 3.4 ± 1.6).There was no evidence of a premature LH surge in either group,but two patients appeared to have a poor response in the leuprolideacetate group (group I). There were 11 pregnancies (21.2%) afterthe use of leuprolide acetate and 12 pregnancies (25.0%) inthose given leuprolide acetate depot; no statistical differenceexisted between these two groups. Thus, an s.c. low-dose leuprolideacetate depot injection may offer a useful alternative for pituitarysuppression in ovarian stimulation for IVF.     

A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.

Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur.     

Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization

Gonadotrophin-releasing hormone agonists (GnRHa) are widely used in in-vitro fertilization (IVF) for the prevention of a premature rise in luteinizing hormone (LH) concentrations. However, the administration of GnRHa during the follicular phase may also impair subsequent luteal function due to retarded recovery of pituitary gonadotrophin secretion. Therefore, luteal supplementation is generally applied. The present study was designed to determine whether a premature LH surge would still be prevented after early cessation of GnRHa during ovarian stimulation and whether subsequent luteal phase LH production would be sufficient to support progesterone synthesis by the corpus luteum. Sixty patients were randomized for three groups: (i) A long GnRHa/human menopausal gonadotrophin (HMG) protocol with luteal support by repeated human chorionic gonadotrophin (HCG) (n = 20), (ii) early follicular phase cessation of GnRHa without luteal support (n = 20), and (iii) a long GnRHa protocol without luteal support (n = 20). Frequent ultrasound and blood sampling was performed during the entire IVF cycle. Forty normo-ovulatory women served as controls. No premature LH surges were found after early cessation of GnRHa. In this group, some pituitary recovery occurred during the late luteal phase, but this did not affect corpus luteum function. Progesterone concentrations were shown to be dependent on disappearance of the pre-ovulatory bolus of HCG. Pregnancies occurred in all three groups. In conclusion, early follicular phase cessation of GnRHa is still effective in the prevention of a premature rise in LH. Although some pituitary recovery was observed thereafter, corpus luteum function is still abnormal due to early luteolysis.     

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.     

Comparison of HMG/HCG superovulation for AID with or without superactive GnRH agonist

New methods of ovulation induction have been discovered andperfected in recent years. Among others, gonadotrophin-releasinghormone (GnRH) agonists are being used increasingly in the treatmentof ovulatory infertility. In a prospective study, 24 women undergoingartificial insemination with donor sperm (AID) and facing failureof treatment because of ovulation disorders, were treated withhuman menopausal gonadotrophin/human chorionic gonadotrophin(HMG/HCG) superovulation with or without pituitary densensitizationusing a superactive luteinizing hormone-releasing hormone (LHRH)agonist, buserelin (BUS), Suprefact (Hoechst, Frankfurt a/Main,FRG). In 86 cycles stimulated with HMG/HCG no pregnancy occurred,whereas 12 pregnancies occurred in the same group of patientsafter a total of 43 BUS/HMG/HCG stimulation cycles. SuperactiveLHRH agonists have a definite place in the treatment of AIDpatients presenting with refractory ovulation disorders and/orluteal insufficiency.     

Oocyte and embryo quality as well as pregnancy rate in intracytoplasmic sperm injection are not affected by high follicular phase serum progesterone

The effect of elevated serum progesterone concentrations (>1ng/1) on or before the day of human chorionic gonadotrophin(HCG) injection on the outcome of women receiving gonadotrophin-releasinghormone analogue (GnRHa)/ human menopausal gonadotrophin (HMG)for ovarian stimulation prior to intracytoplasmic sperm injection(ICSI) was evaluated. A total of 1275 ICSI cycles were analysedretrospectively. In 53 cycles (4.5%), serum progesterone concentrationswere > 1 ng/ml. Patients in the high progesterone group hadsignificantly higher oestradiol and luteinizing hormone concentrationson the day of HCG injection. The characteristics of the cumulus-coronacell complexes and the nuclear maturity of the oocytes weresimilar in the groups of patients with high and low serum progesteronelevels. Fertilization and cleavage rates as well as embryo qualitywere not different in the two groups. No difference in implantationor clinical pregnancy rates was observed between the high progesteroneand low progesterone groups. Moreover, the cumulative exposureto progesterone during the follicular phase, as expressed bythe area under the curve (AUC), and the duration of exposureto high serum progesterone levels (>1 ng/ml) were not significantlydifferent between pregnant and non-pregnant women in the highprogesterone group. We conclude that in ICSI cycles pretreatedwith GnRHa, increased serum progesterone concentrations on orbefore the day of HCG injection do not affect ICSI outcome.     

The effects of the somatostatin analogue octreotide on ovulatory performance in women with polycystic ovaries

The elevated luteinizing hormone (LH) and androgen concentrationscharacteristic of women with polycystic ovaries (PCO) are consideredcrucial factors in their infertility. The somatostatin analogueoctreotide lowers LH and androgen concentrations in women withPCO. The effects of octreotide given concurrently with humanmenopausal gonadotrophin (HMG) were therefore compared withthat of HMG alone in 28 infertile women with PCO resistant toclomiphene. In 56 cycles of combined HMG and octreotide therapythere was more orderly follicular growth compared with the multiplefollicular development observed in 29 cycles in which HMG wasgiven alone (mean number of follicles > 15 mm diameter onthe day of human chorionic gonadotrophin (HCG) administration:2.5 ± 0.2 and 3.6 ± 0.4 respectively; P = 0.026).There was a significantly reduced number of cycles abandoned(>4 follicles > 15 mm diameter on day of HCG) in patientstreated with octreotide + HMG, so that HCG had to be withheldin only 5.4% of cycles compared to 24.1% with HMG alone (P <0.05). The incidence of hyperstimulation was also lower on combinedtreatment. Octreotide therapy resulted in a more ‘appropriate’hormonal milieu at the time of HCG injection, with lower LH,oestradiol, androstenedione and insulin concentrations. Althoughgrowth hormone concentration was similar on both regimens, significantlyhigher insulin growth factor-I concentrations were observedon the day of HCG in women on combined therapy than on HMG alone.