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.     

Polycystic ovary syndrome: low-dose follicle stimulating hormone administration is a safe stimulation regimen even in previous hyper-responsive patients.

We studied 23 women with polycystic ovarian syndrome (PCOS), resistant to clomiphene citrate, who had a previous history of multifollicular ovarian development on gonadotrophin stimulation. Each woman had one cycle of gonadotrophin-stimulating hormone agonist/human menopausal gonadotrophin (GnRHa/HMG) stimulation and then one cycle of low-dose follicle stimulating hormone (FSH) stimulation. All GnRHa/HMG cycles were multifollicular. On the low-dose FSH protocol, 10 cycles were unifollicular, while two to three follicles were observed in nine cycles, and four cycles were multifollicular. The ovarian hyperstimulation syndrome ensued in one of the FSH cycles versus 13 of the GnRHa/HMG cycles. Despite decreasing luteinizing hormone (LH) levels and increasing FSH levels, androgen levels increased during stimulation on both protocols. There was one pregnancy in the GnRHa/HMG cycles versus six pregnancies following the FSH cycles. In conclusion, low-dose FSH administration seems a safe stimulation regimen with a satisfactory conception rate even in PCOS women with a previous record of multifollicular ovarian development.     

Successful treatment of infertile women with hypothalamic primary and secondary protracted amenorrhoea using gonadotrophin releasing hormone analogue and human menopausal gonadotrophin

Thirty-one women with hypothalamic primary or protracted secondary amenorrhoea were treated with human menopausal gonadotrophin (HMG) in 89 cycles, but adequate follicular growth failed to occur. They were then treated with a gonadotrophin releasing hormone analogue (GnRHa) and HMG in 91 cycles. An adequate ovarian response occurred in 68 cycles (74.7%) and pregnancy occurred in 26 cycles (28.6%). GnRHa and HMG produced an adequate ovarian response in hypothalamic amenorrhoeic patients who failed to respond to HMG alone. The strong initial agonistic effect of GnRHa produced sudden high levels of FSH that might possibly have initiated folliculogenesis which was continued by HMG.     

The synergistic effects of clomiphene citrate and human menopausal gonadotrophin in the folliculogenesis of stimulated cycles as assessed by the gonadotrophin-releasing hormone antagonist Nal-Glu.

Clomiphene citrate (CC), alone or in combination with exogenous gonadotrophins, has been widely used in ovulation induction. CC promotes endogenous release of gonadotrophins, yet when used in combination with exogenous gonadotrophins, its contribution to folliculogenesis is difficult to assess. In order to determine the contribution of CC-induced endogenous gonadotrophin production to the overall ovarian stimulation in cycles treated with CC/human menopausal gonadotrophin (HMG), Nal-Glu, a gonadotrophin-releasing hormone (GnRH) antagonist was administered. Fertile women (n = 10) undergoing ovarian stimulation and oocyte aspiration for the sole purpose of gamete donation were studied. Five women received CC (100 mg daily for 5 days) in conjunction with pure follicle stimulating hormone (FSH) 150 IU daily. Five women received HMG alone. Nal-Glu (50 micrograms/kg/day) was administered intramuscularly to both groups when the leading follicles reached a mean diameter of 16 mm. Human chorionic gonadotrophin (HCG) 10,000 IU was given when the largest follicles reached a mean diameter of 20-22 mm. A significant fall in serum oestradiol levels was observed in women given CC/FSH (37.9 +/- 7.3%) within the first 24 h of Nal-Glu administration. Serum luteinizing hormone (LH) decreased greater than 20% within 24 h of Nal-Glu administration and remained low throughout the rest of the treatment. No decrease in oestradiol levels was noted in cycles receiving HMG alone. With supplemental FSH, falling oestradiol levels in CC/FSH cycles rebounded and continued to rise until the day after HCG administration. Despite a drop in oestradiol in CC/FSH cycles, the aspirated oocytes exhibited no untoward effects. The fertilization and cleavage rates were similar, and pregnancies occurred in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Another look at co-treatment with growth hormone and human menopausal gonadotrophins in poor ovarian responders

The objective of this study was to evaluate whether a combinedhuman growth hormone (HGH) and human menopausal gonadotrophin(HMG) treatment can improve ovulation induction in poor ovarianresponders. Ten patients aged 28–43 years and requiring> 25 ampoules of HMG for ovulation were admitted to the study.Pituitary growth hormone reserve was evaluated by clonidinestimulation and insulin tolerance tests before commencementof treatment. The patients underwent one treatment cycle withD-tryptophan-6-luteinizing hormone-releasing hormone (D-Trp⁶-LHRH)and HMG and another cycle with D-Trp⁶-LHRH, HMG and HGH. SerumHGH, insulin-like growth factor (IGF)-I and oestradiol weremeasured throughout the two treatment cycles and follicularmaturation was assessed by ultrasonographic studies. All patientstested showed no elevation of their serum HGH concentrationduring a clonidine test, but showed an adequate response duringinsulin tolerance tests. No significant difference was foundin the number of HMG ampoules, duration of treatment, numberof leading follicles, and serum oestradiol concentration betweenthe two treatment cycles. Co-treatment with HGH and HMG didnot improve ovarian performance in poor ovarian responders.No correlation was found between the results of HGH pituitaryfunction tests and the ovarian response to gonadotrophins.     

Induction of the endogenous gonadotrophin surge for oocyte maturation with intra-nasal gonadotrophin-releasing hormone analogue (buserelin): effective minimal dose

From 1985-1987, a total of 34 couples undergoing superovulation for a single in-vitro fertilization (IVF) cycle with clomiphene citrate and purified follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG) were randomly allocated doses of intra-nasal buserelin to induce an endogenous gonadotrophin surge, prior to oocyte collection. The doses ranged from a single 25 microg dose to 100 microg every 4 h for 20 h. In three cycles the treatment was abandoned because of a poor ovarian response. In the remaining 31 cycles buserelin was given to induce the endogenous gonadotrophin surge, but there was evidence of premature luteinization in eight cycles and a premature gonadotrophin surge in four cycles. Although a single dose as low as 40 microg induced a surge and resulted in a pregnancy, a single dose of 50 microg proved the most effective minimal dose consistently to induce a gonadotrophin surge and oocyte maturation. Recent reports using gonadotrophin-releasing hormone (GnRH) analogues to induce a gonadotrophin surge has prompted publication of this previously unpublished data.      

Endocrinology: Ovarian reserve test with the gonadotrophin-releasing hormone agonist buserelin: correlation with in-vitro fertilization outcome

A gonadotrophin-releasing hormone agonist stimulation test determinationof follicle stimulating hormone (FSH) concentrations beforeand 2 h after buserelin injection was carried out in 78 in-vitrofertilization cycles, and compared ith basal FSH concentrationsto predict ovarian response. Ovarian response was quantifiedby the ratio of peak oestradiol concentration divided by thetotal dose of human menopausal gonadotrophin (HMG) administered,the most reproducible parameter in 11 patients who underwenttwo treatment cycles. Stimulation outcome was highly relatedto the buserelin test, the best prognostic Indicator being thesum of FSH concentrations. However, basal FSH con centrationachieved similar correlations, even in those patients aged >35years. Sensitivity, specificity, positive and negative predictivevalues of basal FSH concentration and sum of FSH concentrationswere similar. Low basal concentration and sum of FSH concentrationswere both associated with a better ovarian response. Constructionof receiver operating characteristic curves demonstrated thatbasal FSH concentration was more informative than the sum ofFSH concentrations. Finally, the sum of FSH concentrations didnot increase the prediction of ovarian response variability.We conclude that the buserelin test is strongly predictive ofstimulation outcome, but is no more informative than the usualscreening. We suggest that the performance of other stimulationtests should be clearly compared with that of basal FSH concentration.     

Endocrine responses to gonadotrophins after LHRH agonist administration on cycle days 1-4: prevention of premature luteinization

A treatment regime comprising an intranasally administered luteinizinghormone-releasing hormone (LHRH) agonist analogue (buserelin)on cycle days 1–4, followed by gonadotrophin administration[follicle stimulating hormone (FSH)/human menopausal gonadotrophin(HMG)] resulted in identical oestradiol (E₂) responses comparedwith the reference method using clomiphene citrate (CC) andgonadotrophins. Immediately after analogue administration (day4), buserelin-treated women showed short-lived elevations inserum LH and progesterone concentrations, but in the later follicularphase, the serum LH concentration was lowered compared withthe controls. None of the women treated with analogue displayedelevated serum LH or progesterone concentrations at the timeof injection of human chorionic gonadotrophin. In the earlyluteal phase, these women had higher serum levels of progesteroneand higher progesterone to E2 ratios than the controls, butthe length of the luteal phase was slightly shortened. Hence,in hyperstimulated cycles, 4-day treatment with buserelin causedprofound endocrinological changes: namely, short-term rescueof the corpus luteum, prevention of an endogenous LH rise andpremature luteinization and increased progesterone productionin the early luteal phase     

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization*

The adverse effect of raised luteinizing hormone (LH) concentrationson reproductive outcome suggests that exogenous LH administrationfor ovarian stimulation may not be desirable. The aim of thisstudy was to compare the clinical pregnancy rates between folliclestimulating hormone (FSH) and human menopausal gonadotrophin(HMG) used in in-vitro fertilization (IVF) cycles. A total of232 infertile patients, with a mean duration of infertilityof 67.1 ± 32.9 months, were selected for IVF (femaleage <38 years, FSH <15 IU/1, and total motile sperm count>5x10⁶). A short (flare-up) protocol with daily leuprolideacetate was followed randomly from day 3 with FSH (n = 115)or human menopausal gonadotrophin (HMG; n = 117), at an initialdose of two ampoules per day. A maximum of three embryos wastransferred, and the luteal phase was supported with four dosesof HCG (2500 IU). No differences were observed between the twogroups in any of the cycle response variables except fertilizationrates per oocyte and per patient, both of which were significantlyhigher with FSH. Clinical pregnancy rates per cycle initiated,per oocyte retrieval and per embryo transfer were 19.1, 21.0and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectivelyfor HMG. Whilst these differences were not statistically significant,the results of this interim analysis suggest that HMG may beassociated with a lower clinical pregnancy rate than FSH.     

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.     

In-vitro fertilization and the ovarian hyperstimulation syndrome.

Eight patients who developed severe ovarian hyperstimulation syndrome (OHSS) were identified among 1302 patients undergoing in-vitro fertilization (IVF) over a 1 year period (prevalence of 0.6%); 63% had ultrasonically diagnosed polycystic ovaries (PCO) and 75% were undergoing their first attempt at IVF. Pretreatment with a superactive luteinizing hormone-releasing hormone (LHRH) analogue significantly increased the prevalence of severe OHSS (1.1% versus 0.2%, P less than 0.05) compared with ovarian stimulation with clomiphene citrate and human menopausal gonadotrophin (HMG). The mean serum oestradiol concentration on the day of human chorionic gonadotrophin (HCG) administration was 8200 +/- 2300 pmol/l. A mean of 19.6 +/- 6.8 follicles had been aspirated and 13.1 +/- 7.7 oocytes recovered at transvaginal ultrasound-directed oocyte recovery. All patients had an embryo transfer and luteal support in the form of HCG. The clinical pregnancy rate was 88%, multiple pregnancy rate 71% and implantation rate 63.5 +/- 41.3%. In a group of seven patients who were hospitalized for moderate OHSS during the same period, peak oestradiol levels were significantly lower than in those with severe OHSS (P less than 0.05). Of the group with moderate OHSS, 57% had PCO, the clinical pregnancy rate was 100% and multiple pregnancy rate 43%. Patients with ultrasound-diagnosed PCO have an increased risk of developing OHSS and the dose of HMG administered to them should be minimized. In patients at risk of developing OHSS, progesterone instead of HCG should be used for luteal support. Transfer of a maximum of two embryos or freezing all embryos for transfer in a subsequent cycle may reduce the likelihood of multiple pregnancy.     

Pharmaco-dynamics of human menopausal gonadotrophin (HMG) and follicle-stimulating hormone (FSH). The importance of the FSH concentration in initiating follicular growth in polycystic ovary-like disease

Using a randomized double-blind cross-over design, the pharmaco-dynamicand pharmaco-kinetic properties of ‘pure’ follicle-stimulatinghormone (FSH) (Metrodin) and human menopausal gonadotrophin(HMG) (Pergonal) were studied in 24 women with polycystic ovary-likedisease (PCOD) during induction of ovulation. Fifty-six cycleswere stimulated with FSH and 60 cycles with HMG, according toa standard protocol. Gonadotrophins were administered i.v. ina pulsatile fashion using pulse frequencies of either 30 or120 min. The cycles stimulated with either 30 or 120 min pulseintervals showed no differences among themselves. During thestimulation phase, the FSH and HMG stimulated cycles showedequal and dose dependent FSH concentrations (mean ± SD).The luteinizing hormone (LH) concentrations (mean ± SD)were also equal but unchanged compared to the mean basal concentration.The LH, FSH, total urinary oestrogen excretion, and testosteroneprofiles (mean ± SD) obtained from cycle days –10to 0 as well as the pregnanediol profiles obtained from cycledays 0 to +14 showed no differences either. The occurrence ofan endogenous preovulatory LH surge was significantly more frequentin the cycles stimulated with a pulse interval of 30 min comparedto the cycles stimulated with a pulse interval of 120 min. Theaddition of LH as provided in HMG did not influence the FSHthreshold concentration above which initiation of folliculargrowth occurred, since no differences were found in the FSH‘stable’ concentrations between FSH and HMG stimulatedcycles. However, intra- and inter-individual variation in theFSH ‘stable’ concentration at which follicular growthwas initiated became obvious. It has been hypothesized thateither diminished circulating bioactive FSH or intrafollicularparacrine factors may influence the FSH threshold concentrationabove which the ovary responds with follicular growth.     

Sertoli-Leydig cell tumour in an infertile patient after stimulated ovulation

A 36 year-old infertile female developed a stage IV (FIGO) ovarian carcinoma consisting of a poorly differentiated Sertoli-Leydig cell tumour after receiving one course of ovulation induction with follicle stimulating hormone (FSH), human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG) followed by gonadotrophin-releasing hormone analogue (GnRHa). The patient died of liver metastasis and hepatic failure 4 1/2 months after first diagnosis, despite aggressive treatment consisting of debulking surgery and aggressive adjuvant chemotherapy.      

Endocrinology: Ultrasonic control without hormone determination for ovulation induction in in-vitro fertilization/embryo transfer with gonadotrophin-releasing hormone analogue and human menopausal gonadotrophin

A total of 114 patients admitted to an in-vitro fertilization-embryotransfer programme for the first time, were randomly assignedto the study group or controls. Gonadotrophinreleasing hormoneanalogue (GnRHa) and human menopausal gonadotrophin (HMG) wereused for ovulation induction. The study patients were followedup merely by ultrasonography and the controls by ultrasonographyand serum determinations of oestradiol, progesterone and luteinizinghormone (LH). There was no significant difference in the durationand total amount of HMG used for ovulation induction (10.9 versus11.5 days and 34.8 versus 37.9 ampoules, respectively). Thenumber of oocytes retrieved (11.7 versus 13.4) and the numbersof embryos replaced (2.6 versus 2.8) and cryopreserved (1.9versus 3.3) were also similar. Pregnancy rates were similar.Pregnancy rate per ovum retrieval was 22.2 versus 25% and perembryo transfer 27.2 versus 26.5%. Oestradiol patterns werealso similar. The rate and severity of ovarian hyperstimulationsyndrome were virtually identical. We conclude that ‘ultrasound-only’monitoring of ovulation induction in IVF cycles treated by GnRHa-HMGin the long protocol is as effective and safe as the conventionalultrasound and hormone determination, but far simpler, swifterand more cost-effective     

Is continuation of a gonadotrophin-releasing hormone agonist (GnRHa) necessary for women at risk of developing the ovarian hyperstimulation syndrome?

A total of 28 women scheduled for in-vitro fertilization used buserelin and human menopausal gonadotrophin (HMG) for ovarian stimulation. One group (I) of 17 women was given human chorionic gonadotrophin (HCG 10,000 IU) to trigger ovulation, but the resulting embryos were electively cryopreserved because of the risk (serum oestradiol greater than or equal to 3500 pg/ml) of developing the ovarian hyperstimulation syndrome (OHSS). Six women continued the buserelin therapy in the luteal phase and eleven did not. In group II (n = 11), the HMG injections were discontinued because of an exaggerated ovarian response and the HCG was omitted. Six of these women continued the buserelin injections until the onset of menses and five did not. In both groups, the ovarian response to induction of ovulation (serum oestradiol concentrations and number of follicles) was similar for those who did or did not continue buserelin therapy. There was no difference in the rate of ovarian quiescence (weekly fall in serum oestradiol concentration following the stimulation) between those women who did or did not continue the buserelin therapy in either group. The serum luteinizing hormone concentrations remained low in all women in both groups. We conclude that the omission of buserelin therapy after discontinuing the HMG in women at risk of developing OHSS does not affect subsequent ovarian quiescence.     

Endocrinology: Development and applications of luteinizing hormone-releasing hormone antagonists in the treatment of infertility: an overview

Luteinizing hormone-releasing hormone (LHRH) plays a crucialrole in controlling the ovarian cycle in women. By modificationof the molecular structure of this decapeptide, analogues weresynthesized with agonistic or antagonistic effects on the gonadotrophiccells of the anterior pituitary gland. The agonists, after aninitial stimulatory effect (‘flare up’), lead todesensitization of the gonadotrophic cells and a reduction inthe number of LHRH receptors on the cell membrane (‘down-regulation’),while the antagonists produce an immediate effect by competitiveblockade of the LHRH receptors. After administration of LHRHantagonists, the serum levels of FSH and LH decrease withinhours. Nevertheless, the adenohypophysis maintains its responsivenessto an LHRH stimulus (‘pituitary response’) afterpretreatment with an antagonist. This different pharmacologicalmechanism of LHRH antagonists makes possible new approachesto ovarian stimulation and to the therapy of sex steroid dependentdiseases. The premature LH surge, the main cause of cancellationduring induction of superovulation in assisted reproductiontechnology (ART) programmes, can be abolished by short termapplication of an LHRH antagonist associated with a reducedhuman menopausal gonadotrophin (HMG) requirement for ovarianstimulation. A future approach to ART might be based on thecombination of pretreatment with an LHRH antagonist and ovulationinduction by native LHRH or an agonist. The severe side effectsencountered with early LHRH antagonists, such as anaphylactoidreactions due to histamine release, are almost completely eliminatedin modern antagonists, especially Cetrorelix which is presentlyused clinically in controlled phase II clinical studies.     

Endocrinology: The role of luteinizing hormone in human follicle development and oocyte fertility: evidence from in-vitro fertilization in a woman with long-standing hypogonadotrophic hypogonadism and using recombinant human follicle stimulating hormone

To evaluate the relative importance of follicle stimulatinghormone (FSH) and luteinizing hormone (LH) in follicular developmentand oocyte fertility in the human species, the use of recombinanthuman FSH, human menopausal gonadotrophin (HMG), and very highlypurified urinary human FSH (FSH-HP) plus oestradiol valeratefor ovarian stimulation and in-vitro fertilization (IVF) werecompared in three cycles in a woman with isolated congenitalgonadotrophin deficiency who had never been treated with ovarianstimulating agents. The total number of ampoules of gonadotrophinsused was lower in the HMG treatment cycle. Ovarian responseand IVF outcome in the three treatment cycles were as follows:(i) HMG cycle: normal follicular growth, normal pattern of oestradioland inhibin through the menstrual cycle, high fertilizationrate (93%); (ii) recombinant FSH cycle: normal follicular growth,low oestradiol and abnormal inhibin, finally poor rate of fertilization(28%); (iii) FSH-HP plus oestradiol valerate cycle: normal folliculargrowth, normal pattern of inhibin and poor fertilization rate(27%). Luteal plasma progesterone concentrations were much higherin the HMG treatment cycle. This case shows that FSH is theonly factor required in order to induce follicular growth inthe human, although LH or a product derived from its actionmay assist in order to achieve full follicular maturity andoocytes capable of fertilization. Though oestradiol might havea mediatory role in the process of follicular maturation, ourresults favour a direct primary role of LH in complete maturationof the follicle.     

The optimum dose and mode of administration of luteinizing hormone releasing hormone analogue in in-vitro fertilization: a comparison of three regimens.

Three regimens for administration of the luteinizing hormone releasing hormone analogue (LHRHa), buserelin, were compared in terms of pituitary down-regulation prior to ovarian stimulation for in-vitro fertilization (IVF). Thirty-three patients who had failed to conceive in previous IVF cycles were randomly divided into three groups. Patients in Group I (n = 11) received intranasal (i.n.) buserelin 200 micrograms four hourly for 21 days; patients in Group II (n = 11) received subcutaneous (s.c.) buserelin 500 micrograms twice a day for 7 days, followed by 500 micrograms daily for 14 days; patients in group III (n = 11) received (s.c.) buserelin 500 micrograms three times a day for 7 days. In all three groups administration of buserelin was continued until serum oestradiol levels were less than 100 pmol/l, at which time human menopausal gonadotrophin (HMG) was commenced. All the patients achieved pituitary down-regulation after seven days of treatment with buserelin, except for four patients who developed ovarian cysts and two with polycystic ovarian disease. The total dose of HMG used and the ongoing pregnancy rate were not significantly different between the three groups. A much higher proportion of patients in Group I developed side-effects and found their treatment disruptive to their life-style. Our results suggest that patient variables (e.g. polycystic ovaries, ovarian cysts) rather than the dose and mode of administration of buserelin, are the major determinant of the length of time needed for pituitary down-regulation. The s.c. route is preferable and the smallest dose of buserelin that will produce pituitary down-regulation should be used.     

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.