Cumulative conception and live birth rates after the treatment of anovulatory infertility: safety and efficacy of ovulation induction in 200 patients

An analysis was performed on the cumulative conception rates,cumulative live birth rates and adverse effects of ovulationinduction in patients with anovulatory infertility attendinga single unit over an 11-year period. A total of 200 patientswere included, 103 with clomiphene-resistant polycystic ovarysyndrome (PCOS), 77 with hypogonado-trophic hypogonadism (HH)and 20 with weight-related amenorrhoea (WRA). Ovulation inductionwas performed using a number of protocols in which pulsatileluteinizing hormone-releasing hormone was administered s.c.or i.v. and gonadotrophins (human menopausal gonadotrophinsor follicle-stimulating hormone) were administered i.m. Thecumulative conception and live birth rates in the first courseof therapy and after 12 cycles of treatment were, respectively,73.2 and 62.4% in PCOS patients, 82.1 and 65.4% in the HH groupand 95.0 and 85.3% in the WRA group. The miscarriage rates forall courses of treatment were 15.5% in PCOS patients, 22.9%in HH patients and 32.3% in WRA patients which resulted in cumulativelive birth rates that were not significantly different. Themedian number of cycles and ovulations to achieve a pregnancywas 2 in all groups. The multiple pregnancy rate was significantlygreater in women with PCOS (17.9% ) than in women with HH (3.6%, p = 0.0052, 95% CI 5.12–23.36% ) but not WRA (3.2% ,p =0.07, 95%CI 4.35–24.92%). The rate of multiple pregnancyfell after the introduction of monitoring by transvaginal ultrasound.Correction of anovulatory infertility by appropriately selectedovulation induction regimens results in cumulative conceptionand live birth rates indistinguishable from normal     

Ovulation induction using s.c. pulsatile gonadotrophin-releasing hormone: effectiveness of different pulse frequencies

To determine the ovarian response to a fixed dose of gonadotrophin-releasinghormone (GnRH) administered s.c. at four different pulse frequencies,20 patients with hypothalamic amenorrhoea were treated over41 cycles using a dose of 200 ng/kg/pulse. These patients wererandomly assigned to receive GnRH at pulse frequencies of 60,90, 120 or 180 min. GnRH was administered s.c using portableinfusion pumps. Subjects were paid volunteers with a diagnosisof hypothalamic amenorrhoea. All patients had low to less thandetectable serum concentrations of luteinizing hormone and folliclestimulating hormone on 8 h serial sampling, and normal serumconcentrations of prolactin and androgen, including andro-stenedione,testosterone and dihydroepiandrosterone sulphate. Six of the20 patients were enrolled in the protocol to achieve a pregnancy,while 14 were volunteers using a barrier method of contraception.Highest ovulation rates were achieved using pulse frequenciesof 90 and 120 min (60 and 88% of cycles respectively). Ovulationoccurred significantly less often with frequencies of 60 and180 min (12 and 38% respectively; P 0.05). Pregnancy was achievedin four of the six patients who desired a pregnancy at pulsefrequencies of 90 (three out of three) and 120 (one out of one)min. No pregnancies occurred at pulse frequencies of 60 (noneout of one) and 180 (none out of one) min. When ovulatory cycleswere considered, oestradiol concentrations were not differentamong pulse frequencies but varied significantly between ovulatoryand anovulatory cycles. Integrated luteal progesterone concentrationsfor 90 and 120 min frequencies (118.26 25.89 and 125.15 32.10 ng/ml/luteal phase respectively) were significantly higherthan for 60 and 180 min (80.1 48.2 and 42.75 26.48 ng/ml/lutealphase respectively). Ovulation may be induced by a broad rangeof pulse frequencies. Pulse frequencies of 90 or 120 min fors.c GnRH appear to induce more reliably the sequence of folliculardevelopment, ovulation and normal luteal function than frequenciesof either 60 or 180 min. Significantly higher ovulation ratesoccurred at 90 and 120 min by s.c administered GnRH.     

A systematic review and meta-analysis of randomized controlled trials on metformin co-administration during gonadotrophin ovulation induction or IVF in women with polycystic ovary syndrome

BACKGROUND: A systematic review of randomized controlled trials (RCTs) comparing whether metformin co-administration with gonadotrophins for ovulation induction (OI) with timed intercourse or IVF improves outcome in women with polycystic ovary syndrome (PCOS). METHODS: The quality of reporting of meta-analyses (QUOROM) guidelines were followed. A systematic computerized literature search of three bibliographic databases was performed. RESULTS: Eight RCTs were included in the overall review. Meta-analysis demonstrated that the co-administration of metformin to gonadotrophin OI does not significantly improve ovulation [odds ratio (OR) = 3.27; 95% confidence interval (95% CI) = 0.31-34.72] or pregnancy (OR = 3.46; 95% CI = 0.98-12.2) rates. Metformin co-administration to IVF treatment does not improve pregnancy (OR = 1.29; 95% CI = 0.84-1.98) or live birth (OR = 2.02, 95% CI = 0.98-4.14) rates but reduces the risk of ovarian hyperstimulation syndrome (OHSS) (OR = 0.21; 95% CI = 0.11-0.41, P < 0.00001). CONCLUSIONS: Current data on the use of metformin in the gonadotrophin OI or IVF treatment settings are inconclusive because of the review's failure to exclude an important clinical treatment effect. Further RCTs are necessary to definitively clarify whether metformin co-administration during gonadotrophin OI or IVF will improve the efficacy of these treatments in PCOS women.     

Endocrinology: Luteal function following ovulation induction in polycystic ovary syndrome patients using exogenous gonadotrophins in combination with a gonadotrophin-releasing hormone agonist

The luteal phase was studied in 12 polycystic ovary syndrome(PCOS) patients following ovulation induction using exogenousgonadotrophins combined with a gonadotrophin-releasing hormoneagonist (GnRH-a). Human menopausal gonadotrophin (HMG) was precededby 3 weeks of treatment with GnRH-a (buserelin; 1200 µg/dayintra-nasally) and administered in a step-down dose regimenstarting with 225 IU/day i.m. GnRH-a was withheld the day beforeadministration of human chorionic gonadotrophin (HCG; 10 000IU i.m.). Blood sampling and ultrasound monitoring was performedevery 2–3 days until menses. The luteal phase was significantlyshorter in PCOS patients as compared to eight regularly cyclingcontrols: 8.8 (3.3–11.4) days [median(range)] versus 12.8(8.9–15.9) days (P = 0.01). Median peak values for progesteronedid not show significant differences comparing both groups:52.3 (17.1–510.3) nmol/l versus 43.0 (31.2–71.1)nmol/l, respectively (P = 0.8). The interval between the dayof the progesterone peak and return to baseline was significantlyshorter in the PCOS patients than in controls: 2.5 (0.3–4.9)days versus 4.2 (3.9–10.5) days (P < 0.005). Luteinizinghormone (LH) concentrations during the luteal phase as reflectedby area under the curve were significantly lower in PCOS ascompared to controls: 4.4 (1.6–21.0) IU/l x days and 49.0(27.8–79.6) IU/l x days, respectively (P < 0.001).In conclusion, patients with PCOS may suffer from insufficientluteal phases after ovulation induction using HMG/HCG in combinationwith a GnRH-a. The corpus luteum apparently lacks the supportof endogenous LH and may be stimulated only by the pre-ovulatoryinjection of HCG. Potential involvement of adjuvant GnRH-a medicationor HCG itself in luteal suppression of endogenous gonadotrophinsecretion, and the importance of luteal function for pregnancyrates following treatment, warrant further studies.     

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     

Pure FSH for ovulation induction in patients with polycystic ovary syndrome and resistant to clomiphene citrate therapy

Twenty-nine infertile women with polycystic ovary disease whichwas resistant to therapy with clomiphene citrate underwent acombined treatment for follicle recruitment consisting of pureFSH during the first days of the cycle and HMG during the lastdays of the follicular phase. Sixty cycles were stimulated ofwhich 83% were ovulatory. Eighteen pregnancies were achieved(36% of cycles, 62% of patients). The multiple pregnancy ratewas 39%. Twelve cycles (20%) showed the ovarian hyperstimulationsyndrome (OHS) although seven of these resulted in full termdeliveries. There were no miscarriages among the patients studied.     

Highly purified FSH is as efficacious as recombinant FSH for ovulation induction in women with WHO Group II anovulatory infertility: a randomized controlled non-inferiority trial

BACKGROUND: The objective of this study was to demonstrate non-inferiority of a highly purified urinary follicle stimulating hormone (HP-FSH) preparation compared with a recombinant (rFSH) preparation with respect to ovulation rate (primary end-point). METHODS: This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-FSH (n=73) or rFSH (n=78) using a low-dose step-up protocol. The non-inferiority limit was prespecified at -20%. RESULTS: The ovulation rate was 85.2% (51/62) with HP-FSH and 90.9% (60/66) with rFSH (per-protocol population), and non-inferiority was demonstrated [95% confidence interval: -16.9; 5.6]. No differences were noted between groups in number of follicles>or=12 mm, >or=15 mm or >or=18 mm, mono-follicular development, pregnancy rates, endometrial thickness, number of ovarian stimulation syndrome cases or frequency of injection site reactions/pain. The singleton live birth rate was 15% in both groups (11/73 with HP-FSH and 12/78 with rFSH). CONCLUSIONS: This urinary HP-FSH preparation is non-inferior compared with a rFSH preparation with respect to ovulation rate in anovulatory WHO Group II women failing to ovulate or conceive on clomiphene citrate.     

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.     

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.     

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.     

Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success

BACKGROUND: Although laparoscopic ovarian drilling (LOD) hasbeen widely used to induce ovulation in women with polycysticovarian syndrome (PCOS), predicting the clinical response tothis treatment remains to be elucidated further. This studywas carried out to identify factors that may help to predictthe outcome of LOD. METHODS: This retrospective study included200 patients with anovulatory infertility due to PCOS who underwentLOD between 1990 and 2002. The influence of the various patients'pre-operative characteristics on the ovulation and pregnancyrates after LOD was evaluated. In addition, women were dividedinto two or three categories according to the severity of eachof the various clinical and biochemical parameters of PCOS.The success rates were compared between the categories of eachfactor using contingency table analyses. Multiple logistic regressionanalysis was used to identify independent predictors of successof LOD. RESULTS: Women with body mass index (BMI) 35 kg/m²,serum testosterone concentration 4.5 nmol/l, free androgen index(FAI) 15 and/or with duration of infertility >3 years seem tobe poor responders to LOD. In LOD responders, serum LH levels>10 IU/l appeared to be associated with higher pregnancy rates.CONCLUSION: Marked obesity, marked hyperandrogenism and/or longduration of infertility in women with PCOS seem to predict resistanceto LOD. High LH levels in LOD responders appear to predict higherprobability of pregnancy.     

Current and future status of ovulation induction in polycystic ovary syndrome

Great progress has been achieved during the last 20 years inthe field of ovulation induction in patients with polycysticovary syndrome (PCOS). Clomiphene citrate remains the firstline of treatment for all anovulatory women with PCOS, sincein properly selected patients the cumulative pregnancy rateapproaches that in normal women. Human urinary gonadotrophinshave been used extensively for ovulation induction but the developmentof low-dose regimens has opened a new era in the managementof anovulation related to PCOS. This article discusses the mainadvantages and disadvantages of the principal methods and regimenscurrently used for ovulation induction in patients with PCOSincluding clomiphene citrate, gonadotrophins, pulsatile gonadotrophin-releasinghormone (GnRH) and GnRH agonists. It also discusses new drugsdiscovered recently, particularly recombinant gonadotrophinsand GnRH antagonists, and provides some thoughts regarding theiruse in future protocols. Finally, based on the discovery ofnew ovarian substances which specifically control luteinizinghormone (LH) secretion, this article develops assumptions onpossible implications of these substances in the pathophysiologyof PCOS and their potential use in the management of the syndrome.     

Circulating immunoreactive and bioactive follicle stimulating hormone concentrations in anovulatory infertile women and during gonadotrophin induction of ovulation using a decremental dose regimen

Our purpose was to determine whether decreased follicle stimulatinghormone (FSH) activity, either systemic or at the follicularlevel, is involved in impaired follicle growth associated withnormogonadotrophic anovulation. To differentiate between thepossible levels of disturbance, bioactive (BIO-FSH; using thein-vitro rat granulosa cell aromatase bioassay) and immunoreactive(IRMA-FSH) FSH serum concentrations of three groups of subjectswere compared: (i) 172 normogonadotrophic anovulatory infertilewomen during baseline conditions, (ii) 22 clomi-phene-resistantpolycystic ovary syndrome patients undergoing ovulation inductionby exogenous gonadotrophins using a decremental dose regimen,and (iii) nine regularly cycling controls. BIO-FSH [13.2 (range0.8–29.5) IU/1] and IRMA-FSH [4.4 (range 1.2–9.3)IU/1] concentrations in anovulatory women during baseline conditionswere significantly lower than maximum concentrations reachedduring the follicular phase in controls [18.7 (13.2–23.4)and 6.4 (5.7–10.0) IU/1 respectively], but were not significantlydifferent from initial concentrations in controls [10.4 (7.2–19.6)and 4.8 (2.8–8.2) IU/1 respectively]. Moreover, concentrationsof IRMA-FSH and BIO-FSH were negatively correlated (r = –0.25,P = 0.01, and r = –0.24, P = 0.02 respectively) with theinterval between last vaginal bleeding and blood sampling. Maximumconcentrations of IRMA-FSH [7.6 (3.9–10.9) IU/1] duringovulation induction by gonadotrophins were not significantlydifferent from [6.4 (5.7–10.0) IU/1] concentrations incontrols, whereas maximum BIO-FSH concentrations [13.5 (8.7–17.4)versus 18.7 (13.2–23.4) IU/1] were significantly lower.Our findings suggest that (i) circulating FSH does not reachconcentrations that are sufficient to induce normal follicledevelopment in anovulatory women during base-line conditions,and (ii) the FSH threshold for ovarian stimulation of this patientgroup is not different from normal     

Anovulatory infertility*

The ESHRE Capri Workshop group first arrived at a working definitionof anovulatory infertility, then discussed the diagnoses, theadvantages and disadvantages of the available treatments forthe various categories of infertility, namely hyperprolactinaemicanovulation, hypogonadotrophic hypogonadism and normogonadotrophicanovulation including polycystic ovary syndrome.     

Ovulation induction in polycystic ovarian disease by pure FSH (Metrodin). A comparison between chronic low-dose pulsatile administration and i.m. injections

A randomized cross-over study was performed to assess the value of pulsatile versus i.m. administration of pure FSH in polycystic ovarian disease. All patients admitted to the study had failed to respond to treatment with clomiphene citrate, while four had also been unsuccessfully treated with i.m. Pergonal. Sixteen cycles with i.m. FSH and 15 cycles with pulsatile s.c. FSH were analysed. The results showed no statistically significant differences in the dosage, the rate of ovulation or pregnancy rate. Hyperstimulation occurred in 30% of both the treatment groups. It is concluded that chronic low-dose pulsatile administration of pure FSH (Metrodin, Serono) has no advantage over chronic low-dose i.m. administration.     

Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: rationale, results, reflections and refinements

Low-dose follicle stimulating hormone (FSH) regimens for induction of ovulation for women with polycystic ovaries have succeeded in reducing the rate of ovarian hyperstimulation syndrome (OHSS) almost to nil and the rate of multiple pregnancies to a minimum of 6%. This has been achieved by reaching, but not exceeding, the threshold level of FSH, starting with a daily dose of 75 IU for 14 days, using small incremental dose rises where necessary, and inducing uniovulation in 70% of cycles. Conception rates are as good, if not better, than those achieved with conventional therapy. The miscarriage rate is still relatively high (20-25%) and obese women fare worse. Serum oestradiol concentrations and the number of large and intermediate follicles on the day of human chorionic gonadotrophin administration are much lower, in parallel with lower serum FSH concentrations. Inhibin values increase with the rise in serum FSH concentrations but those of luteinizing hormone decrease steadily throughout the follicular phase. New data using recombinant hFSH (rhFSH), rather than urinary gonadotrophin as the ovarian stimulant, demonstrate that treatment time is shortened. However, the ideal regimen has still to be formulated.     

Ovulation induction in perspective

It has been suggested recently that, in some quarters, IVF be offered as first-line therapy to all infertile couples, regardless of the type of infertility. Hence, the time was thought right to scrutinise the results and complications of ovulation induction for anovulatory infertile couples. In addition to examining the outcome of conventional treatment with gonadotrophins and clomiphene citrate, special attention has been paid to the suggested improvement of results by taking into account the influence of obesity and the use of a low-dose gonadotrophin protocol. The possible contribution of more recent additions to the armamentarium such as insulin sensitizers and aromatase inhibitors, although still at an infant stage, are promising. Attention has been given to the prevention and treatment of ovarian hyperstimulation syndrome. The use of intra-uterine insemination (IUI) as an adjuvant to induction of ovulation and controlled ovarian hyperstimulation (COH) is examined. The very firm conclusion has been reached that, taking into account efficiency, complication rate and cost of treatment, at this stage, women with hypogonadotrophic hypogonadism or polycystic ovary syndrome should be offered accepted methods of ovulation induction and that couples with 'unexplained' or 'multifactorial subfertility' should still be exposed to COH with IUI and only after the failure of these therapies, be offered IVF.     

Induction of follicular growth and production of a normal hormonal milieu in spite of using a constant low dose of luteinizing hormone in women with hypogonadotrophic hypogonadism

This study was designed to examine ovarian performance, i.e.follicular growth, normal steroidogenesis and luteal phase function,following the administration of multiple increasing doses ofhuman follicle stimulating hormone (FSH) with a constant lowdose of luteinizing hormone (LH) in women with isolated hypogonadotrophichypogonadism. Human meno–pausal gonadotrophin (HMG) wasused in the first treatment cycle, starting with 150 IU of LHand 150 IU of FSH per day, for 7 days. The dose was increaseddaily with 75 IU of LH and 75 IU of FSH for another 7 days ifno response was detected by serial ultrasound measurements andserumoestradiol determinations. In the second treatment cycle,a constant dose of 75 IU of LH (using HMG) was administeredper day and up to 150 IU of FSH (using urofollitrophin) wassupplemented. If no response was detected after 7 days of treatment,the dose of FSH was increased. For the final stage of ovulationinduction, human chorionic gonadotrophin (HCG) was administeredin the presence of at least one follicle >17 mm in diameterbut with no more than three follicles >16mm in diameter.To verify the adequacy of the luteal phase, a pharmacokinetic/pharmacodynamicstudy of -HCG, oestradiol and progesterone was performed followingthe second treatment cycle only. Ovarian stimulation using aconstant dose of 75 IU of LH and increasing doses of FSH upto 225 IU, resulted in normal follicular growth and hormonalmilieu. Both women showed normal luteal phase oestradiol andprogesterone production and both women conceived following thesecond treatment cycle     

Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group II anovulatory infertility: a randomized controlled study

BACKGROUND: The contribution of the LH activity in menotrophin preparations for ovulation induction has been investigated in small trials conducted versus FSH preparations. The objective of this study was to demonstrate non-inferiority of highly purified urinary menotrophin (HP-HMG) versus recombinant FSH (rFSH) with respect to the primary outcome measure, ovulation rate. METHODS: This was a randomized, open-label, assessor-blind, multinational study. Women with anovulatory infertility WHO Group II and resistant to clomiphene citrate were randomized (computer-generated list) to stimulation with HP-HMG (n=91) or rFSH (n=93) using a low-dose step-up protocol. RESULTS: The ovulation rate was 85.7% with HP-HMG and 85.5% with rFSH (per-protocol population), and non-inferiority was demonstrated. Significantly fewer intermediate-sized follicles were observed in the HP-HMG group (P<0.05). The singleton live birth rate was comparable between the two groups. The frequency of ovarian hyperstimulation syndrome and/or cancellation due to excessive response was 2.2% with HP-HMG and 9.8% with rFSH (P=0.058). CONCLUSIONS: Stimulation with HP-HMG is associated with ovulation rates at least as good as a rFSH in anovulatory WHO Group II women. LH activity modifies follicular development so that fewer intermediate-sized follicles develop. This could have a positive impact on the safety of ovulation induction protocols.     

Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea

Pulsatile administration of gonadotrophin releasing hormone(GnRH) is a very effective treatment for induction of ovulationin hypothalamic amenorrhoea (HA). Thirty-seven women have beentreated for a total of 117 cycles which resulted in 42 pregnancies–fourtreatment failures occurred. If these cycles are excluded, the42 pregnancies were obtained within 2.3 cycles. One twin pregancyoccurred and no hyperstimulation was observed. The treatmentwas administered intravenously with a dosage schedule basedon the grading of HA. We concluded that pulsatile GnRH was safeand very successful in induction of pregnancy in HA. Other indications(polycystic ovary syndrome and luteal phase defect) remain muchless suitable for this treatment.