A direct healthcare cost analysis of recombinant LH versus hMG supplementation on FSH during controlled ovarian hyperstimulation in the GnRH-antagonist protocol.

PURPOSE: We have previously published a retrospective matched-case control study comparing the effect of recombinant LH (r-hLH) versus highly purified human menopausal gonadotropin (hMG) supplementation on the follicle-stimulating hormone (FSH) during controlled ovarian hyperstimulation (COH) in the GnRH-antagonist protocol. The result from that study showed that the cumulative live birth rate (CLBR) was significantly higher in the r-hLH group (53% vs. 64%, p = 0.02). In this study, we aim to do a cost analysis between these two groups based on our previous study. METHODS: The analysis consisted of 425 IVF and ICSI cycles in our previous study. There were 259 cycles in the r-hFSH + hMG group and 166 cycles in the r-hFSH + r-hLH group. The total cost related to the treatment of each patient was recorded. Probabilistic sensitivity analysis (PSA) and a cost-effectiveness acceptability curve (CEAC) were performed and created. RESULTS: The total treatment cost per patient was significantly higher in the r-hFSH + r-hLH group than in the r-hFSH + hMG group ($4550 ± 798.86 vs. $4290 ± 734.6, p = 0.003). However, the mean cost per live birth in the r-hFSH + hMG group was higher at $8052, vs. $7059 in the r-hFSH + r-hLH group. The CEAC showed that treatment with hFSH + r-hLH proved to be more cost-effective than treatment with r-hFSH + hMG. Willingness-to-pay was evident when considering a hypothetical threshold of $18,513, with the r-hFSH + r-hLH group exhibiting a 99% probability of being considered cost-effective. CONCLUSION: The cost analysis showed that recombinant LH is more cost-effective than hMG supplementation on r-hFSH during COH in the GnRH-antagonist protocol.

Cost-effectiveness analysis of recombinant human follicle-stimulating hormone alfa(r-hFSH) and urinary highly purified menopausal gonadotropin (hMG) based on data from a large German registry.

This was a retrospective real-world evidence analysis of the costs per live birth for reference recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG-HP), based on data from a German in vitro fertilization registry (RecDate). Pregnancy and live birth rates from the RecDate real-world evidence study over three complete assisted reproductive technology (ART) cycles using the same gonadotropin drug were used as clinical inputs. Costs related to ART treatment and to drugs were obtained from public sources. Treatment with r-hFSH-alfa resulted in higher adjusted cumulative live birth rates versus hMG-HP after one (25.3% vs. 22.3%), two (30.9% vs. 27.5%), and three (31.9% vs. 28.6%) ART cycles. Costs per live birth were lower with r-hFSH-alfa versus hMG-HP after one (€17,938 vs. €20,054), two (€18,251 vs. €20,437), and three (€18,473 vs. €20,680) ART cycles. r-hFSH-alfa was found to be a cost-effective strategy compared with hMG-HP over three cycles.

Cost-Effectiveness Analysis of the Gonadotropin Treatments HP-hMG and rFSH for Assisted Reproductive Technology in France: A Markov Model Analysis.

OBJECTIVES: The objectives of this study were to assess (1) the expected cost of a live birth (LB) after in vitro fertilization with two different gonadotropin treatments [high purified human menopausal gonadotropin (HP-hMG) and recombinant follicle-stimulating hormone (rFSH)] as the single cost variable, and (2) the cost effectiveness of HP-hMG relative to rFSH in the context of the routine practice of assisted reproductive technology (ART) in France. METHODS: A Markov model was developed to simulate the therapeutic management, the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) courses, and the effects of complications in hypothetical cohorts of 30,000 patients undergoing IVF/ICSI with fresh embryo transfer (up to four attempts) using data from the MERIT and MEGASET clinical trials or from French routine ART practice. RESULTS: The cost per LB was estimated at €12,145 and at €14,247 with HP-hMG and rFSH, respectively, using efficacy data from published clinical trials. The resulting incremental cost-effectiveness ratio (ICER) was - €11,616 per LB. HP-hMG was less expensive by around €15.0 million and more effective by 1289 additional LBs. Using French clinical data, the cost per LB was €16,415 and €18,7531 with HP-hMG and rFSH, respectively. The ICER for HP-hMG versus rFSH was estimated at - €7,719 per LB with a saving of about €8.54 million and 1097 additional LBs. Deterministic sensitivity analyses showed that the main ICER drivers were the LB rate, followed by the total gonadotropin doses. The probabilistic sensitivity analysis indicated that HP-hMG was the dominant strategy in 71.2% of cases using the clinical trial data and in 50.2% of cases using the French data. CONCLUSION: This analysis indicates that compared with rFSH, HP-hMG is less costly for IVF/ICSI management from the French healthcare payer's viewpoint. The results of the present Markov model analysis are consistent with previous findings in other European countries.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

BACKGROUND AND OBJECTIVE: Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F®) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur®) and urinary follicle-stimulating hormone (uFSH, Fostimon®)-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. METHODS: A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. RESULTS: The mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167-6151), €5990 for hp-HMG (95 % UI €5498-6488) and €5760 for uFSH (95 % UI €5256-6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4-44.3 %), 33.9 % (95 % UI 26.2-41.5 %) and 34.1 % (95 % UI 25.9-41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. CONCLUSION: The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate-Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness Analysis.

BACKGROUND: Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives. METHODS: A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children. RESULTS: The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967). CONCLUSION: This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients.

Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation.

BACKGROUND: Gonadotropins are protein hormones which are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. There is still a lively debate on which type of gonadotropin medication should be used, either human menopausal gonadotropin or recombinant follicle-stimulating hormone. The objective of the study was to perform a systematic review of the recent literature to compare recombinant follicle-stimulating hormone to human menopausal gonadotropin with the aim to assess any differences in terms of efficacy and to provide a cost evaluation based on findings of this systematic review. METHODS: The review was conducted selecting prospective, randomized, controlled trials comparing the two gonadotropin medications from a literature search of several databases. The outcome measure used to evaluate efficacy was the number of oocytes retrieved per cycle. In addition, a cost evaluation was performed based on retrieved efficacy data. RESULTS: The number of oocytes retrieved appeared to be higher for human menopausal gonadotropin in only 2 studies while 10 out of 13 studies showed a higher mean number of oocytes retrieved per cycle for recombinant follicle-stimulating hormone. The results of the cost evaluation provided a similar cost per oocyte for both hormones. CONCLUSIONS: Recombinant follicle-stimulating hormone treatment resulted in a higher oocytes yield per cycle than human menopausal gonadotropin at similar cost per oocyte.

Assessment of deoxyribonucleic acid fragmentation index, testicular volume, semen parameters, and hormone profile in gonadotropin-treated men with hypogonadotropic hypogonadism.

OBJECTIVE: To study the sperm deoxyribonucleic acid (DNA) fragmentation index (DFI), testicular volume, semen parameters, and hormone profile in human chorionic gonadotropin (hCG)- and human menopausal gonadotrophin (hMG)-treated patients with hypogonadotropic hypogonadism (HH) with and without a successful pregnancy. METHODS: This is a cross sectional study. The study initially included 81 patients with HH and azoospermia at the Infertility Unit of Royan Institute between 2010 and 2012. Fifty-eight of 81 patients achieved >1 × 10(6) sperm/mL during hCG and hMG therapy. These 58 patients were divided into the following 2 groups: 20 patients with HH who achieved pregnancy in response to hCG/hMG (responders, 16 naturally and 4 by intrauterine insemination) and 38 gonadotropin-treated patients with HH with failed pregnancy (nonresponders, 29 naturally, 5 by intrauterine insemination, 1 by in vitro fertilization, and 3 by intracytoplasmic sperm injection). Sperm DNA fragmentation was visualized by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Average of DFI (responders: 13.45 ± 0.64; nonresponders: 21.92 ± 0.86), age, body mass index, testis volume semen parameters, and follicle-stimulating hormone, luteinizing hormone, and testosterone levels in the 2 groups were calculated. Cut-off point for DFI was determined by receiver operating curve analysis (17.5%). CONCLUSION: It was shown that DFI in responders is significantly lower than DFI in nonresponders (P <.001), and duration of hCG and hMG therapy in responders is significantly higher than those of nonresponders (P <.05). DFI could be predictive of conception (P <.001; odds ratio 0.57; 95% confidence interval 0.417-0.778). It can be concluded that despite low sperm quality, especially sperm concentration in these patients, decreasing sperm DNA damage may result in successful fertilization.

Sequential clomiphene citrate/hMG versus hMG for ovulation induction in clomiphene citrate-resistant women.

OBJECTIVE: This study was designed to compare sequential clomiphene citrate/hMG regimen to hMG regimen for ovulation induction in clomiphene citrate-resistant women. STUDY DESIGN: A comparative prospective study. PATIENTS AND METHODS: Ninety infertile women were randomized to receive either sequential CC/hMG regimen (45 women) or low-dose step-up protocol of hMG (45 women). All participants had received at least six consecutive cycles of clomiphene citrate for ovulation induction within the last year before inclusion in this study, but they did not conceive. The CC/hMG regimen group received clomiphene citrate 100 mg/day for 5 days, followed by hMG 75 IU for 4 days. The hMG group received low-dose step-up protocol for 10-14 days. To detect the number and size of the follicles, TVS was done on cycle day 8 and repeated daily or every other day according to follicular development. When one to three follicles reached a diameter ≥18 mm, hCG injection was scheduled. Before hCG injection, the E2 level and endometrial thickness were evaluated. ß-hCG levels were measured on cycle day 22. RESULTS: There was no significant difference between the two studied groups regarding the demographic data, sperm parameters, and day 3 FSH, LH and estradiol. Also, there was no significant difference between the two studied groups regarding endometrial thickness, number of mature follicles, peak of E2 before hCG injection and number of cases that developed ovarian cyst or OHSS. The dose of gonadotropins used was significantly low in the CC/hMG group compared to the hMG group (295.2 ± 75.5 vs. 625.3 ± 65.0, respectively), and the pregnancy rate was significantly high in the CC/hMG group compared to the hMG group [12 (26.7 %) vs. 3 (6.7 %), respectively, p < 0.05]. CONCLUSION: The sequential CC/hMG regimen is as effective as hMG regimen for ovulation induction, produces satisfactory pregnancy results and reduces the treatment cost.

Modified super-long down-regulation protocol improved the outcome of in vitro fertilization-embryo transfer in infertile patients.

OBJECTIVE: To investigate the outcome of in vitro fertilization and embryo transfer (IVF-ET) in special infertile patients following modified super-long down-regulation protocol combined with human menopausal gonadotropin (HMG) stimulation. METHODS: Ninety-nine special patients (42 with endometriosis, 35 with PCOS, and 22 with insufficient down-regulation) who underwent modified super-long down-regulation protocol in 2008 were retrospectively analyzed. Gonadotropin releasing hormone analogues (GnRHa, 1.5 mg) was injected intramuscularly in mid-luteal phase twice and HMG was started 25 days later after the second GnRHa injection. Conventional IVF-ET was performed as routine procedure. The clinical outcomes were compared with those of 122 similar patients in the same period. RESULTS: After modified super-long down-regulation, (1) in endometriosis patients, the average gonadotropin (Gn) used was (32.33 +/- 15.11) ampoules, duration of medication was (10.57 +/- 1.88) days, the progesterone (P) level on hCG day was (0.78 +/- 0.44) microg/L, and the clinical pregnancy rate (CPR) was 73.8%; (2) in PCOS patients, the average Gn used was (28.57 +/- 12.07) ampoules, the duration of medication was (11.71 +/- 2.07) days, the P level at hCG day was (0.65 +/- 0.39) microg/L, and the clinical pregnancy rate was 65.7%; (3) in insufficient down-regulation patients, the average Gn used was (26.22 +/- 12.07) ampoules, the duration of medication was (10.01 +/- 1.77) days, the P level at hCG day was (0.71 +/- 0.50) microg/L, and the clinical pregnancy rate was 72.7%. Compared with patients using regular down-regulation protocol, the clinical pregnancy rate was improved significantly and the cost decreased obviously. The clinical pregnancy rate significantly improved compared with that of routine long down-regulation groups. CONCLUSION: Revised super-long protocol plus HMG is a cost-effective controlled ovary hyperstimulation (COH) regimen for infertile patients with endometriosis, PCOS and insufficient down-regulation.

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

OBJECTIVE: To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. DESIGN: An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. SETTING: Fifty-three fertility clinics in 13 European countries and Israel. PATIENT(S): Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. INTERVENTION(S): Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). MAIN OUTCOME MEASURE(S): Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. RESULT(S): HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. CONCLUSION(S): Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

A prospective, randomised, controlled clinical study on the assessment of tolerability and of clinical efficacy of Merional (hMG-IBSA) administered subcutaneously versus Merional administered intramuscularly in women undergoing multifollicular ovarian stimulation in an ART programme (IVF).

BACKGROUND: Multifollicular ovarian stimulation (MOS) is widely used in IVF and the compliance to treatment is deeply influenced by the tolerability of the medication(s) used and by the ease of self-administration. This prospective, controlled, randomised, parallel group open label, multicenter, phase III, equivalence study has been aimed to compare the clinical effectiveness (in terms of oocytes obtained) and tolerability of subcutaneous (s.c.) self-administered versus classical intramuscular (i.m.) injections of Merional, a new highly-purified hMG preparation. METHODS: A total of 168 normogonadotropic women undergoing IVF were enrolled. Among them, 160 achieved pituitary suppression with a GnRH-agonist long protocol and were randomised to MOS treatment with Merional s.c. or i.m. They started MOS with a standard hMG dose between 150-300 IU, depending upon patient's age, and underwent a standard IVF procedure. RESULTS: No statistically significant difference in the mean number of collected oocytes (primary endpoint) was observed between the two study subgroups (7.46, SD 4.24 vs. 7.86, SD 4.28 in the s.c. and i.m. subgroups, respectively). As concerns the secondary outcomes, both the pregnancy and the clinical pregnancy rates were comparable between subgroups. The incidence of adverse events was similar in the two groups (2.4% vs. 3.7%, respectively). Pain at injection site was reported only the i.m. group (13.9% of patients). CONCLUSION: Merional may be used by s.c. injections in IVF with an effectiveness in terms of retrieved oocytes that is equivalent to the one obtained with i.m administration and with a better local tolerability. With the limitations due to the sample size af this study, s.c. and i.m. administration routes seem to have the same overall safety.

An economic evaluation of highly purified HMG and recombinant FSH based on a large randomized trial.

Public funding for IVF is increasingly being challenged by health authorities in an attempt to minimize health service costs. In light of treatment rationing, the need to consider costs in relation to outcomes is paramount. To assess the cost implications of gonadotrophin treatment options, an economic evaluation comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) has been conducted. The analysis is based on individual patient data from a large randomized controlled trial (n = 731) in a long agonist IVF protocol. The economic evaluation uses a discrete event simulation model to assess treatment costs in relation to live births for both treatments based on published UK costs. After one cycle the mean costs per IVF treatment for HP-HMG and rFSH were pound2396 (95% CI pound2383-2414) and pound2633 ( pound2615-2652), respectively. The average cost-saving of pound237 per IVF cycle using HP-HMG allows one additional cycle to be delivered for every 10 cycles. With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound8893 compared with pound11,741 for rFSH (P < 0.001). The cost-saving potential of HP-HMG in IVF was still apparent after varying critical cost parameters in the probabilistic sensitivity analysis.

[A case of Kallmann syndrome: usefulness of the aging male's symptoms rating scale for assessment of subjective symptoms].

We report a case of Kallmann syndrome in which the aging male's symptoms rating scale (AMS) was useful for assessment of subjective symptoms. A 30-year-old male was admitted to Tsukuba University Hospital with a complaint of delayed puberty in May 2003. He presented with hypogonadism, gynecomastia and anosmia. The plasma levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were very low. However, the LH-releasing hormone test and human chorionic gonadotropin (hCG) loading test identified normal function of pituitary and Leydig cell. After 12 months of treatment with hCG and human menopausal gonadotropin (hMG), the amount of pubic hair and the volume of testes had increased as well as the level of serum testosterone. The total score of AMS after treatment has been improved from 39 to 20 as compared with that before treatment.

Urofollitropin and ovulation induction.

Anovulation is a common cause of female infertility. Treatment for women with anovulation is aimed at induction of ovulation. Ovulation induction with follicle-stimulating hormone (FSH) is indicated in women with WHO type II anovulation in whom treatment with clomifene citrate (clomifene) has failed. The majority of these women have polycystic ovary syndrome. The major disadvantages of ovulation induction with FSH are the risk of ovarian hyperstimulation syndrome and the risk of higher order multiple pregnancies. To reduce the rate of complications due to multiple follicular development, FSH should be administered using a chronic low-dose protocol with small dose increments. In women with WHO type I anovulation, an exogenous supply of luteinizing hormone (LH) is required to achieve an adequate follicular response to FSH treatment. Thus, ovulation induction with FSH is not the treatment of choice in these women. FSH is a hormone that stimulates follicle growth and oocyte maturation. Endogenous FSH is produced by the pituitary gland and exists as a family of isohormones exhibiting distinct oligosaccharide structures. FSH for exogenous administration is derived from urine or is produced as recombinant FSH. The commercially available FSH products all contain different mixtures of FSH isoforms. To determine the effectiveness of urofollitropin (urinary-derived FSH), a comparison with the other available gonadotropins was made (i.e. recombinant FSH and human menopausal gonadotropin). Urofollitropin and recombinant FSH appear to be equally effective and well tolerated for ovulation induction. Human menopausal gonadotropin is comparably effective to urofollitropin in terms of pregnancy outcomes. It remains unclear whether human menopausal gonadotropins have a higher risk of overstimulation and ovarian hyperstimulation syndrome compared to urofollitropin in women with polycystic ovary syndrome. In practice, recombinant products are more convenient to use but are also more expensive. Therefore, if availability is not an issue but costs are, there is still a place for the use of urofollitropins for ovulation induction.

Comparison of controlled ovarian stimulation with human menopausal gonadotropin or recombinant follicle-stimulating hormone.

OBJECTIVE: To carefully examine the features of controlled ovarian stimulation performed with recombinant FSH-alpha or hMG. DESIGN: Controlled, prospective, randomized comparison of fixed gonadotropin regimens. SETTING: Academic research institution. PATIENT(S): Fifty infertile patients who were candidates for IUI. INTERVENTION(S): Patients were randomized to receive a fixed regimen of recombinant FSH-alpha (150 IU/day, 25 patients) or hMG (150 IU/day, 25 patients), after GnRH-agonist suppression (long regimen). MAIN OUTCOME MEASURES: Daily measurements of serum LH, immunoreactive FSH, hCG, E(2), P, and T. Transvaginal pelvic ultrasound every 2 days. Pregnancy and abortion rates. Cost of medications. Two recombinant FSH-alpha-treated patients did not respond. Despite matched daily FSH dose, duration of treatment (hMG 10.8 +/- 0.4 vs. recombinant FSH-alpha 12.4 +/- 0.5 days), gonadotropin dose (21.7 +/- 0.8 vs. 25.3 +/- 1.3 ampoules), gonadotropin cost (288 +/- 10 vs. 1,299 +/- 66 /cycle), serum P levels, and small preovulatory follicle number were significantly lower, and LH, hCG, immunoreactive FSH levels, and larger follicles on day 8 were significantly higher in hMG-treated patients. The pregnancy, abortion, and twin pregnancy rates did not differ. CONCLUSION: The hMG administration was associated with: [1]. increased serum LH activity and immunoreactive FSH levels during treatment; [2]. reduced signs of premature luteinization; [3]. differential modulation of folliculogenesis; [4]. lower treatment duration, gonadotropin dose, and cost; and [5]. clinical outcome comparable to recombinant FSH-alpha.

Sequential treatment of metformin and clomiphene citrate in clomiphene-resistant women with polycystic ovary syndrome: a randomized, controlled trial.

BACKGROUND: Recognition of the importance of insulin resistance in clomiphene-resistant women with polycystic ovary syndrome (PCOS) has led to the use of insulin sensitizers. METHODS: A randomized, controlled trial was conducted to compare efficacy of sequential treatment with metformin and clomiphene citrate with conventional gonadotrophins. Sixty clomiphene-resistant women with PCOS were randomized to two groups (n = 30 each), using computer-generated tables. Group I received metformin for 6 months, followed by ovulation induction with clomiphene citrate; group II received hMG for ovulation induction. Hormonal profiles were evaluated at the onset and after completion of treatment. RESULTS: There was no significant difference in pregnancy rates between the two groups (16.7 versus 23.3%). In group I, there was a significant improvement in menstrual function and ovulation after treatment (40%, P < 0.001; and 46.7%, P < 0.001), with a significant decrease in fasting insulin levels (P < 0.05). There were no changes in other biochemical parameters. The ovulation rate in group II was 43.3%, with a high drop-out rate. The cost-effective analysis for medications per pregnancy in group I was US$ 71 +/- 3 versus US$ 277 +/- 171 in group II. CONCLUSIONS: Sequential treatment with metformin and clomiphene citrate is an effective and safe option for clomiphene-resistant women with PCOS.

The conflict between effective and affordable health care--a perspective from the developing world.

The recent introduction of recombinant FSH into the clinical management of patients suffering from infertility appears to be associated with several treatment benefits when compared with urinary human menopausal gonadotrophin. However, from the perspective of the developing world the associated increase in cost is a cause for concern--particularly if the "cheaper" urinary gonadotrophins are no longer marketed. The need for infertility care in Africa is significant, but health resources are very limited. The commonest cause of infertility in Africa is tubal disease, so that assisted reproductive techniques, and therefore exogenous gonadotrophins, are central to effective management. The conflict between affordable and effective health care is addressed.

Surgical or medical treatment of polycystic ovary syndrome: a cost-benefit analysis.

With the availability of laparoscopic ovarian cautery, there has been a resurgence in interest in the surgical treatment of clomiphene citrate-resistant polycystic ovary syndrome (PCOS). Comparison of ovulation and pregnancy rates has found no difference in success rates between ovarian cautery and gonadotropin ovulation induction for such women. We have therefore compared the cost of laparoscopic ovarian cautery with that of a typical cycle of gonadotropin ovulation induction, and also found that there is little difference. Because of the potential advantages of ovarian cautery, we recommend this surgery as the next line of treatment if clomiphene citrate fails to induce ovulation in PCOS patients, before gonadotropins are introduced.

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

BACKGROUND: The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). METHODS: A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. RESULTS: The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. CONCLUSION: rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.