Successful induction of ovulation and completed pregnancy using recombinant human luteinizing hormone and follicle stimulating hormone in a woman with Kallmann's syndrome

The induction of ovulation in women with hypogonado-trophichypogonadism requires follicle stimulating hormone (FSH) forfollicular growth and both FSH and luteinizing hormone (LH)to induce optimal follicular steroidogenesis. The developmentof human recombinant FSH and LH means that individually tailoreddoses of both hormones can be used with the aim of inducingunifollicular ovulation. This report describes the use of recombinanthuman FSH and LH for the induction of ovulation and conceptionin the second cycle of treatment, and subsequently a successfullycompleted pregnancy in a woman with Kallmann's syndrome.     

A prospective, randomized comparison of ovulation induction using highly purified follicle-stimulating hormone alone and with recombinant human luteinizing hormone in in-vitro fertilization.

The commercial availability of highly purified, s.c. administered urinary follicle stimulating hormone (FSH) preparations for ovarian stimulation marked the beginning of a new era in the treatment of infertility. As these new formulations contain essentially no luteinizing hormone (LH), supplemental LH may be needed for optimal folliculogenesis. It was the aim of this pilot study to compare fertilization rates, embryo morphology, implantation rates and pregnancy outcomes prospectively in two age-matched patient groups: women who received highly purified FSH (FSH-HP) (n = 17), and women who received FSH-HP plus recombinant human LH (rhLH, n = 14) throughout ovarian stimulation. All patients received mid-luteal pituitary down-regulation with s.c. gonadotrophin-releasing hormone agonist (GnRHa) (leuprolide). Mean implantation rates were 26.9 and 11.9% in the FSH-HP only and FSH-HP + rhLH groups respectively. The mean clinical pregnancy/initiated cycle rate was 64.7 and 35.7% for the FSH-HP only and FSH-HP + rhLH patients respectively. FSH-HP patients and FSH-HP + rhLH patients achieved clinical pregnancy/transfer rates of 68.8 and 45.5% respectively. One patient in the FSH-HP + rhLH group had a spontaneous abortion; no pregnancy losses occurred in the FSH-HP only group. There were more cancellations for poor ovarian response among FSH-HP + rhLH patients (n = 3) than among FSH-HP patients (n = 1). The trend toward better pregnancy outcomes among patients who received FSH-HP without supplemental rhLH did not reach statistical significance. It is postulated that appropriate endogenous LH concentrations exist despite luteal GnRHa pituitary suppression, thereby obviating the need for supplemental LH administration.     

Modulation of folliculogenesis and steroidogenesis in women by graded menotrophin administration

BACKGROUND: To test the effects of progressively decreasing dosages of exogenous LH we combined various amounts of HMG, containing FSH, LH and HCG, and highly purified (HP) FSH to treat 120 GnRH agonist-suppressed infertile female patients as candidates for controlled ovarian stimulation (COS). METHODS: Subjects were randomly assigned to four treatment groups that received the following daily i.m. gonadotrophin regimens: A, FSH 150 IU only; B, FSH 150 IU and LH activity 37.5 IU; C, FSH 150 IU and LH activity 75 IU; D, FSH 150 IU and LH activity 150 IU. FSH dose adjustments were allowed only after the 14th treatment day. Monitoring included transvaginal ultrasound at 2-day intervals and daily determinations of LH, FSH, estradiol (E(2)), progesterone, testosterone and HCG. RESULTS: Duration of COS was significantly shortened in patients receiving at least 75 IU daily of LH activity. Small (<10 mm diameter) pre-ovulatory ovarian follicle occurrence was inversely correlated with LH activity dose administered (r = -0.648, P < 0.0001) and serum HCG levels (r = -0.272, P < 0.01) but not to serum LH levels. Serum testosterone levels were positively correlated to the LH activity dose administered (r = 0.313, P < 0.001), while serum progesterone levels were positively correlated to the FSH dose administered (r = 0.447, P < 0.00001) but not to the LH activity dose administered. CONCLUSIONS: Firstly, HCG content considerably contributes to HMG activity; secondly, menotrophin LH activity content can reduce in a dose-dependent manner the occurrence of small pre-ovulatory follicles; and finally, contrary to common belief, enhanced FSH stimulation rather than LH activity appears to cause premature follicle luteinization during COS.     

Ovarian response in repetitive cycles induced by menotrophin alone or combined with gonadotrophin releasing hormone analogue

The number of oocytes retrieved for in-vitro fertilization (IVF) has a major influence on the number of embryos developed and pregnancy success. This study was designed to investigate the ovarian response in the same patient under the same and different stimulation protocols. In group A, 19 patients underwent two consecutive cycles, both stimulated with human menopausal gonadotrophin (HMG). Group B comprised 27 patients who experienced two successive cycles treated with the combination of long-acting gonadotrophin releasing hormone analogue (GnRHa) and HMG. Group C included 27 patients whose first cycle was stimulated with HMG alone, and their second with a GnRHa/HMG combination. The mean number of HMG ampoules administered and the duration of treatment were similar in both cycles of group A and B patients while in group C, both the amount and duration of HMG administration were significantly higher and longer in the combined protocol compared to HMG alone. This study demonstrates an identical ovarian response using the same mode of stimulation in repeated cycles, and a significantly improved response with the GnRHa/HMG combination compared with HMG alone in the same patient.     

Endocrine and follicle characteristics of cycles with and without endogenous luteinizing hormone surges during superovulation induction with pulsatile follicle-stimulating hormone

The induction of superovulation in women with human gonadotrophinsmay result in blockage of the endogenous luteinizing hormone(LH) surge, but the reasons for this are not known. Ten normallyovulating women with longstanding infertility volunteered forthis study. They were treated with 225 IU follicle-stimulatinghormone (FSH) daily s.c. in a pulsatile manner (28 IU every3 h) starting on cycle day 2. Serum FSH and oestradiol levelsincreased and serum LH levels decreased significantly duringthe FSH treatment, as compared to their spontaneous cycles.Only five women displayed an LH surge during the FSH treatment.Serum FSH and LH levels during treatment were significantlylower and the number of follicles 12–15 mm in diameterand their total fluid volume was significantly greater in thecycles without an endogenous LH surge. Basal LH levels in thecycles without an LH surge increased soon after the end of theFSH treatment (cycle day 18), while FSH levels were still verylow without any incremental tendency. These results suggestthat a high number of small follicles may have a suppressiveeffect on both tonic and mid-cycle gonadotrophin secretion.Furthermore, the LH suppressive mechanism seems to be differentfrom that of the FSH.     

Recombinant hormones: Effect of recombinant human luteinizing hormone versus human chorionic gonadotrophin: effects on ovulation, embryo quality and transport, steroid balance and implantation in rabbits

A total of 40 New Zealand female rabbits which had been givenfollicular stimulation and artificial insemination received50 IU of either recombinant human luteinizing hormone (rhLH;n = 20) or human chorionic gonadotrophin (HCG; n = 20) to induceovulation. In each hormone group, 10 animals were killed 72h later to study the ovulatory process and the number, location,morphological quality and variation in the degree of developmentof recovered embryos. Pre-ovulatory and post-ovulatory oestradioland progesterone concentrations were determined in these 10animals; the remaining 10 animals of each group were killedat 14 days to study implantation up to day 14. At 72 h the numberof luteinized follicles and the total number of embryos in therhLH group were lower than in the HCG group, and the numberof pre-ovulatory follicles was higher. The percentage of goodquality embryos was higher with rhLH, whereas the percentageof degenerated embryos was lower. Oviductal transit of the embryoswas slower and variation in the degree of embryo developmentgreater after HCG. Progesterone concentrations were comparablewith pre-ovulatory concentrations at 24 h in the rhLH group,but not in the HCG group where they increased. In the studyperformed at 14 days, the implantation rate was significantlyhigher with rhLH versus HCG. These observations suggest thatrhLH induces a lower number of follicles to ovulate than doesHCG, probably due to its shorter half-life; however, the betterembryo quality produced by rhLH may ultimately lead to a betterimplantation rate; rhLH may mimic the physiological endogenousLH surge more closely than HCG.     

Effect of cyclofenil on hormonal dynamics, follicular development and cervical mucus in normal and oligomenorrhoeic women.

Cyclofenil is a triphenylethylene derivative, similar in structure to clomiphene citrate, which is used to induce ovulation in anovulatory women. The effects of cyclofenil on a group of 10 normal cyclic and 10 oligomenorrhoeic subjects were examined in a double blind controlled cross-over study. Both groups of women were administered either cyclofenil or, following a washout cycle, a placebo in two treatment cycles. Urinary oestrone and pregnanediol excretion were measured daily and ultrasound scans performed to assess follicular development. Frequent sampling of blood was performed on day 6 to study luteinizing hormone (LH) and follicle stimulating hormone (FSH) pulsatile release. Cervical mucus changes and sperm-cervical mucus interaction were studied after identification of the LH peak. There were no significant differences between cyclofenil and placebo cycles in the following: ovulation rates, daily urinary oestrone and pregnanediol excretion, the number or size of developing follicles, LH pulsatility (parameters studied: number of peaks, pulse interval, pulse amplitude, pulse area and mean nadir LH), mean FSH level on day 6, cervical mucus and sperm-cervical mucus interaction. In view of our inability to demonstrate an effect on any parameter of endocrine function in normal and oligomenorrhoeic women, these results throw doubt on the therapeutic value of cyclofenil in its present dosage and formulation.     

Reevaluation of the roles of luteinizing hormone and follicle-stimulating hormone in the ovulatory process.

Circulating levels of luteinizing hormone (LH) are essential for the production of steroid hormones that regulate the timing of ovulation and target tissue responses, as well as maintenance of the corpus luteum and therefore early pregnancy. Clinical and basic science observations show that elevated levels of serum LH during the follicular phase of the menstrual cycle are not only unnecessary for follicular maturation but are deleterious to normal reproductive processes. These elevations may occur as a result of administration of exogenous LH or through an endogenous pathological process (i.e. polycystic ovarian disease, PCOD). Resting levels of LH, synergizing with locally produced IGFs, inhibin and perhaps other growth factors, are adequate for normal follicular growth and steroidogenesis. Elevations in serum LH above these resting levels may result in increased androgen production that diminishes follicular function and reduces early embryo viability. Elevated LH levels during the preovulatory period may also negatively influence post-ovulatory events such as conception and implantation. With these facts in mind, the best results for ovulation induction would be expected with purified follicle-stimulating hormone (FSH) administration to women following gonadotrophin releasing hormone (GnRH) down-regulation. It is hoped that this review provides the reader with an analysis of the complex series of events that regulate normal follicular maturation. The reevaluation of the two cell-two gonadotrophin theory suggests that during the preovulatory period, resting levels of LH are adequate for normal follicular maturation. Indeed, overstimulation of the ovary with excessive amounts of LH may diminish the ability of that target organ to produce fertile ova.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrinology: Induction of pre-ovulatory gonadotrophin surge with gonadotrophin-releasing hormone agonist compared to pre-ovulatory injection of human chorionic gonadotrophins for ovulation induction in intrauterine insemination treatment cycles

The clinical outcome of intrauterine insemination (IUI) treatmentcycles employing a gonadotrophin-releasing hormone agonist [GnRHa,triptorelin (Decapeptyl)] or human chorionic gonadotrophin (HCG)for ovulation induction was compared. A group of 48 patientspresenting with amenorrhoea, oligomenorrhoea or unexplainedinfertility were all treated with human menopausal gonadotrophins(HMG) from day 5 of the cycle, on an individualized schedule.They were then randomly divided into two groups to receive eithera single s.c. injection of 0.1 mg triptorelin or a single i.m.injection of 10 000 IU HCG after follicular maturation. IUIwas performed 24 and 48 h following the injection. A transitoryincrease in serum luteinizing hormone and follicle stimulatinghormone concentrations was achieved following injection of GnRHa.A total of 24 patients received 72 treatment cycles with GnRHa,producing 11 conceptions (15.3%) and two abortions (18.2%),resulting in a term pregnancy rate of 13.6%. There were fourcases of grade 3–4 ovarian hyperstimulation syndrome (OHSS),two of which were conception cycles. In all, 24 patients underwent68 cycles treated with HCG, producing 18 conceptions (26.5%)and six abortions (33.3%), resulting in a term pregnancy rateof 19.0%. There were eight cycles of grade 3–4 OHSS, twoof which were conception cycles. These results show that ans.c. injection of a relatively low dose of GnRHa can be as effectiveas HCG in producing pregnancy in IUI treatment cycles.     

The effects of a gonadotrophin-releasing hormone agonist on treatment with low dose follicle stimulating hormone in polycystic ovary syndrome

The objective of this study was to investigate whether the incidenceof monofollicular growth during stimulation with low dose folliclestimulating hormone (FSH) changes when adjuvant gonadotrophin-releasinghormone agonist (GnRHa) pre-treatment is administered in polycysticovary syndrome (PCOS). One group of patients (group 1) sufferingfrom clomiphene resistant PCOS was stimulated with low doseFSH. The results were compared with those from another groupof similar patients (group 2) subsequently stimulated with lowdose FSH combined with GnRHa. In group 1 15 patients had 39stimulation cycles performed; in group 2 13 patients had 33stimulation cycles performed. In group 1 44% of cycles weremonofollicular, whilst the corresponding figure in group 2 was14% (P = 0.04). Evidence was found for postponed atresia ingroup 2. In both groups 1 and 2 interindividual and intra-individualvariability of the FSH dose inducing follicular growth wereobserved. We concluded that during the use of GnRHa, stimulationwith low dose FSH less frequently resulted in monofolliculargrowth, possibly due to postponed atresia. Furthermore, theuse of GnRHa does not abolish the inter- and intra-individualvariability of the FSH dose inducing ongoing follicular growth.     

Gonadotrophin-releasing hormone agonist and ovarian hyperstimulation syndrome in assisted reproduction

The available literature concerning the association betweengonadotrophin-releasing hormone agonist and ovarian hyperstimulationsyndrome has been reviewed and the different patterns by whichthis agent may contribute to the development of such iatrogeniccomplication has been elicited, and guidelines have been presentedfor prevention of this malady. Gonadotrophin-releasing hormoneagonist acts directly on human granulosa cells, probably inits own dose-dependent manner. The extent of this action isprobably subjected to follicular maturation stage and to thedegree of gonadotrophin pre-treatment. Various agonist effectsin assisted reproduction may be implicated in the developmentof ovarian hyperstimulation syndrome: a higher amount of menotrophin;premature luteinization prevention; ‘flare-up’ effect;and a higher pregnancy rate. Different methods for preventionof ovarian hyperstimulation syndrome may be attempted: (i) allembryo cryopreservation with luteal phase reinitiation of agonist;(ii) avoidance of ovulatory human chorionic gonadotrophin (HCG)and continuation of agonist; (iii) cancellation of ovulatoryHCG, prolongation of agonist and later recommencement of menotrophin;(iv) pre-ovulatory LH surge triggering by agonist instead ofthe conventional HCG. Gonadotrophin-releasing hormone agonistmay affect the steroidogenic ovarian stroma directly and suchinteraction may aggravate the development of ovarian hyperstimulationsyndrome.     

Genetic variant of luteinizing hormone in women with a history of recurrent miscarriage

Because the biological and clinical significance of a geneticvariant of luteinizing hormone (LH) is unclear, we thereforeevaluated the occurrence of variant LH in women with a historyof recurrent spontaneous abortion (RSA) and related it to specificLH concentrations, luteal function and pregnancy outcome. Ofthe 85 RSA women, 30 (35.3%) had variant LH (28 heterozygousand two homozygous), and 55 women (64.7%) a normal wild-typeLH ratio. These frequencies are similar to those reported fromthe general Finnish population. No significant differences wereobserved in specific LH concentrations based on LH status (7.2± 1.4 IU/l, mean ± SEM, variant LH, versus 8.5± 1.6 IU/l, wild-type LH). Variant LH was twice as commonin women with body mass index (BMI) > 25 kg/m² (9/15, 60.0%)than in those with BMI 25 kg/m² (21/70, 30.0%, P < 0.05).The presence of variant LH was not associated with any cleareffect on endocrine variables such as endometrial maturationor mid-luteal phase oestradiol and progesterone concentrations.During follow-up, 23 women with variant LH (76.7%) and 41 withwild-type LH (74.5%) became pregnant: 14 miscarried (21.9%,six with variant LH and eight with wild-type LH) and two hadectopic pregnancies, whereas 48 (75.0%) succeeded (17 with variantLH and 31 with wild-type LH). LH concentrations before pregnancywere similar in women with a successful outcome (8.0 ±1.3 IU/l) or with a miscarriage also in that pregnancy (7.4± 1.4 IU/l). In conclusion, variant LH is common in RSAwomen who are relatively overweight (BMI > 25 kg/m²) butits presence is not reflected in endometrial maturation andmiscarriage rates.     

Comparison of a rapid, quantitative and automated assay for urinary luteinizing hormone (LH), with an LH detection test, for the prediction of ovulation

The prediction of ovulation is necessary for oocyte aspiration in a spontaneous cycle and can be reliably achieved only by measuring luteinizing hormone (LH). Since radioimmunoassays of LH take too long for repeated measurements on the same day, we evaluated the possibility of adapting a rapid and fully automated assay of serum LH for use with urine samples. The study group comprised spontaneously ovulating women (38 cycles) who requested artificial insemination. Their serum oestradiol (E2) levels, ultrasound profile (US) and thrice daily urinary LH levels were determined from day 10 of their menstrual cycle. These patients were followed until US signs of follicular rupture were recorded. In all patients, a well-defined LH peak was measured in the urine. This peak lasted 12-15 h and was followed in 35 cycles (no US available for 3) by follicular rupture 9-51 h later. The data were grouped according to the time of the LH peak on day 0. Patients experiencing an LH peak between 0300 h and 0700 h on day 0 had significantly lower levels of E2 on day 0 compared to those with an LH peak between 2200 h and midnight. This is due to the fact that in the patients with an LH peak between 0300 h and 0700 h, E2 levels were already decreasing (from day 1 to day 0), whereas in those with the LH peak between 2200 h and midnight E2 levels were still increasing on the morning of day 0. We conclude that the 30-min IMX LH assay is a reliable, rapid and readily acceptable method for measuring urinary LH and for the prediction of ovulation.     

Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage

Polycystic ovary syndrome is associated with hypersecretionof luteinizing hormone (LH) which has been implicated in theaetiology of early pregnancy loss. Although 82% of women withrecurrent early loss have polycystic ovaries on ultrasound imaging,random serum LH concentrations are normal. In the present study,we have obtained further information from serial samples concerningthe cyclical patterns of gonadotrophin and sex steroid secretionin these women. Twenty-one women with recurrent early pregnancyloss and 10 multiparous controls were investigated; 81% of themand one of ten control subjects had polycystic ovaries. Meanmid-follicular and mid-luteal serum LH and follicle stimulatinghormone (FSH) levels were similar in both groups. Seventeenwomen with pregnancy loss had either raised urinary LH excretionor a premature LH surge; one control subject had a prematureLH surge. Total LH excretion during the cycle and mean follicularphase serum testosterone was significantly greater with earlypregnancy loss than in the control group, the difference inLH being greatest in the early luteal phase. Urinary oestrone-3-glucuronideexcretion was raised in the early luteal phase of the cyclein the group with early pregnancy loss; there was no differencebetween the groups in pregnanediol-3-glucuronide excretion.These data demonstrate abnormalities in LH secretion in 81%of women with recurrent fetal loss. Inappropriately raised LHlevels may have adverse effects on the developing oocyte orendometrium either directly, or indirectly by causing an elevationin testosterone and oestrogen levels.     

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.     

Endocrinology:Follicle stimulating hormone (FSH) dynamics of low dose step-up ovulation induction with FSH in patients with polycystic ovary syndrome

Pharmacodynamics of follicle stimulating hormone (FSH) werestudied during low dose step-up gonadotrophin therapy in patientswith polycystic ovary syndrome (PCOS). To obtain stable levelsof FSH, Metrodin was administered i.v. By making daily determinations,the FSH concentration was slowly increased in steps of 1 IU/I.A total of 16 patients were treated for a maximum of three treatmentcycles. Out of 38 treatment cycles, in 26 (68%) a single dominantfollicle developed. The overall ovulation rate was 78%. FSHconcentrations were evaluated with regard to intra–andinter–individual variability of the FSH threshold andwith regard to the relationship between FSH concentrations,FSH dose and treatment outcome. The high variability of theFSH threshold, ranging from 5.7 to 12 IU/I, appeared to be mainlya function of inter-individual variability. Higher FSH concentrationswere associated with multifollicular growth as opposed to monofolliculargrowth, whereas the increases in concentration from a substimulatingto a stimulating level were not. Multifollicular growth mightthus be associated with a higher elevation of FSH concentrationabove the threshold. Different patterns of FSH concentrationin the course of the growth phase of the dominant follicle inmono– compared to multifollicular cycles suggested a differencein the effect of endogenous FSH on the plasma concentration.Endogenous feedback on FSH release may therefore still playa role during treatment with exogenous FSH     

A comparative prospective study of a chronic low dose versus a conventional ovulation stimulation regimen using recombinant human follicle stimulating hormone in anovulatory infertile women

The efficacy and safety of a chronic low dose (group A) anda conventional (group B) stimulation regimen of recombinanthuman follicle stimulating hormone (r-HFSH) were compared in103 WHO Group II infertile women with clomiphene citrate-resistantanovulation. Mono- or bifollicular development was induced in88.1% of patients in group A compared with 76.1% in group B.Ovulation and pregnancy rates were higher in group A (71.4%and 33.3%, respectively) than in group B (63.0% and 20%), butthese differences were not statistically significant. Additionally,the total number of follicles that were >10 mm diameter waslower in group A than group B (3.0 ± 2.6 versus 6.3 ±6.5; P < 0.0001), as was the oestradiol concentration (504± 477 pg/ml versus 988 ± 740 pg/ml; P < 0.03).The median dose of FSH (75 IU ampoules) used per cycle was 11ampoules in group A and 12.5 in group B. In terms of the incidenceof ovarian hyperstimulation syndrome, no differences were recordedbetween the two groups. The results demonstrated that r-HFSHis effective and safe in both these treatment protocols. Thechronic low dose regimen was associated with a trend towardsa higher rate of mono- or bifollicular development, withoutjeopardizing the incidence of pregnancy.     

Discrimination between chronological and ovarian age in infertile women aged 35 years and older: predicting pregnancy using basal follicle stimulating hormone, age and number of ovulation induction/intra-uterine insemination cycles

A marked decline in fertility rates has been demonstrated inwomen >35 years of age. We have previously demonstrated theimportance of basal follicle stimulating hormone (FSH) concentrationsplus chronological age to predict pregnancies in women aged40 years undergoing ovula-tion induction therapy. The purposeof the current study was to extend our previous study and determinethe impact of age, basal FSH concentrations and ovulation induction/intra-uterine insemination (IUI) treatment cycles on pregnancyrates in infertile women aged 35 years. This prospective observationalstudy was performed at a tertiary university fertility centre.Assessments of basal hormonal status and ovulation inductionprotocols were performed. The main outcome measured was clinicalpregnancies. A total of 770 treatment cycles in 179 women aged35 years were analysed. The impact of basal FSH concentrationson treatment outcomes could be bifurcated into a favourablegroup (FSH 23 mlU/ml) and a poor prognosis group (FSH 24 mlU/ml).A multivariate logistic regression model was generated whichaccurately predicted pregnancies. There was a high degree ofcorrelation between predicted pregnancies and observed pregnancies(r = 0.86). We conclude that age, number of treatment cyclesand the interaction term basal FSH x age are useful and significantpredictors of pregnancies in patients aged 35 years undergoingovulation induction/IUl therapy.     

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.     

First established pregnancy and birth after induction of ovulation with recombinant human follicle-stimulating hormone in polycystic ovary syndrome

This case report describes the first established pregnancy andbirth after induction of ovulation with recombinant human follicle-stimulatinghormone (FSH) in a woman suffering from chronic clomiphene-resistantanovulation due to polycystic ovary syndrome (elevated serumluteinizing hormone and testosterone concentrations togetherwith polycystic ovaries). Starting on day 3 of a progestagenwithdrawal bleeding, 75 IU of rFSH was administered i.m.dailyuntil a single preovulatory follicle was seen upon transvaginalultrasound examination at day 13. Ovulation was induced by asingle i.m. administration of 10 000 IU of human chorionic gonadotrophin,after which aviable singleton pregnancy was revealed at a gestationalage of 6 weeks. The course of pregnancy and labour was uneventfuland no abnormalities were found upon a paediatric examination.