Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany.

BACKGROUND: This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany. METHODS: Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle). RESULTS: Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP. CONCLUSIONS: This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.

A large, multicentre, observational, post-marketing surveillance study of the 2:1 formulation of follitropin alfa and lutropin alfa in routine clinical practice for assisted reproductive technology.

BACKGROUND: Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) both have a role to play in follicular development during the natural menstrual cycle. LH supplementation during controlled ovarian stimulation (COS) for assisted reproductive technology (ART) is used for patients with hypogonadotropic hypogonadism. However, the use of exogenous LH in COS in normogonadotropic women undergoing ART is the subject of debate. The aim of this study was to investigate characteristics of infertile women who received the 2:1 formulation of follitropin alfa and lutropin alfa (indicated for stimulation of follicular development in women with severe LH and FSH deficiency) in German clinical practice. METHODS: A 3-year, multicentre, open-label, observational/non-interventional, post-marketing surveillance study of women (21-45 years) undergoing ART. Primary endpoint: reason for prescribing the 2:1 formulation of follitropin alfa and lutropin alfa. Secondary variables included: COS duration/dose; oocytes retrieved; fertilization; clinical pregnancy; ovarian hyperstimulation syndrome (OHSS). RESULTS: In total, 2220 cycles were assessed; at least one reason for prescribing the 2:1 formulation was given in 1834/2220 (82.6%) cycles. Most common reasons were: poor ovarian response (POR) (39.4%), low baseline LH (17.8%), and age (13.8%). COS: mean dose of the 2:1 formulation on first day, 183.1/91.5 IU; mean duration, 10.8 days. In 2173/2220 (97.9%) cycles, human chorionic gonadotrophin was administered. Oocyte pick-up (OPU) was attempted in 2108/2220 (95.0%) cycles; mean (standard deviation) 8.0 (5.4) oocytes retrieved/OPU cycle. Fertilization (≥1 oocyte fertilized) rates: in vitro fertilization (IVF), 391/439 (89.1%) cycles; intracytoplasmic sperm injection (ICSI)/IVF + ICSI, 1524/1613 (94.5%) cycles. Clinical pregnancy rate: all cycles, 25.9%; embryo transfer cycles, 31.3%. OHSS: hospitalization for OHSS, 8 (0.36%) cycles, Grade 2, 60 (2.7%), and Grade 3, 1 (0.05%). CONCLUSIONS: In German routine clinical practice, the most common reasons for using the 2:1 formulation of follitropin alfa and lutropin alfa for women undergoing ART were POR, low baseline LH, and age. Severe OHSS incidence was low and similar to that reported previously.

The redesigned follitropin alfa pen injector: results of the patient and nurse human factors usability testing.

OBJECTIVES: A redesigned pen injector for administration of follitropin alfa (follitropin α) has been developed for use in fertility treatment cycles. Pre-summative and summative usability testing was undertaken to assess the risk of dosing errors compared with the existing follitropin α pen. The study also assessed proper use of and dose selection with the redesigned pen. METHODS: Infertile women who were trying to conceive and specialist nurses were recruited from four cities in Germany. Usability goals relating to proper use of the pen device were defined from a risk assessment and further categorized as critical and functional operational goals. Individual, non-interventional, standardized, usability tests were performed with patients and nurses by four experienced research professionals using questionnaires that also included ease-of-use ratings. A non-standardized qualitative analysis of nurse-patient training sessions was performed in the presence of a research professional; reasons for confidence, safety, possible misunderstandings and risks when handling the pen were noted. RESULTS: The overall risk of dosing errors with the redesigned pen was not higher than with the existing pen. No unexpected operational risks and no major concerns regarding the risk of misuse or dosing errors were identified. CONCLUSIONS: The study provides useful practical information on the redesigned pen from both patient and nurse perspectives.

The redesigned follitropin α pen injector for infertility treatment.

INTRODUCTION: Treatment for infertility may require multiple drugs and complex dosing schedules. Available injection devices for patients who require regular injections during treatment are reviewed in this article, focusing on pen injectors used to self-administer recombinant human follicle-stimulating hormone (follitropin α). Following the introduction of the first and second follitropin α pen injectors in the last decade, a third pen injector with improved design for the administration of follitropin α has been developed for use in fertility treatment cycles. AREAS COVERED: This paper presents the results of the dose accuracy testing with this pen injector that was performed in accordance with international standards (EN ISO 11608-1:2000). This overview also provides an understanding of the key features of the redesigned pen injector that are of interest to healthcare professionals. EXPERT OPINION: The availability of an improved injection device for the delivery of follitropin α used during infertility treatment cycles of ovulation induction and assisted reproductive technology offers patients and healthcare professionals new treatment administration options. As fertility treatment cycles involve the use of several injectable gonadotropins, a standard device that could be used for all such treatments would simplify both the administration and the teaching of administration considerably.

Gonadal steroids and affective symptoms during in vitro fertilization: implication for reproductive mood disorders.

Gonadal steroids (GSs) have been associated with the onset of a number of reproductive-related mood disorders in women, in which fluctuating or unstable hormonal levels are postulated to act as the trigger for the destabilization of mood. There is, however, rather limited direct clinical evidence that can link rapidly changing GS levels with the induction of mood symptoms. We aimed to study the effect of controlled and rapid GS fluctuations on mood in an in vivo model. Women undergoing in vitro fertilization (n=108) were assessed for depression and anxiety levels on 3 time points: during a low estradiol and progesterone baseline, during a gonadotropin stimulated estradiol-dominant phase, and after embryo transfer, during a progesterone-dominant low estrogen phase. Plasma levels for estrogen and progesterone were drawn on these time points. Symptoms of depression and anxiety significantly increased from baseline to the high estradiol levels but were not correlated with estrogen. The sharp drop from high estradiol levels at the estradiol-dominant phase to low levels at the progesterone-dominant phase was significantly correlated with rising depression scores. The rise in progesterone levels from low levels at the estradiol-dominant phase to high levels at the progesterone-dominant phase was significantly and inversely correlated with depression scores. This study suggests that the mechanism underlying the role of estrogen in reproductive-related mood disorders involves an abrupt and precipitous drop in its plasma level that can precipitate negative mood states. This finding has implications on the treatment of GS-related mood disorders.

[Differing response to GnRH antagonists in cycles of ovarian hyperstimulation plus intrauterine insemination]. / Diferencia de respuesta a los antagonistas de GnRH en ciclos de hiperestimulación ovárica más inseminación intrauterina.

OBJECTIVE: To compare two flexible protocols of GnRHant in OH plus IUI vs a control group without GnRHant. MATERIALS AND METHODS: Randomized controlled trial 90 infertile patients were analyzed in 116 cycles of IUI. Cycles were randomized in 3 groups; group 1: started GnRHant when the leading follicle reached 14mm, group 2: when it reached 16mm and group 3: without GnRHant hormonal determinations were done during OH. Main outcomes were: premature LH raise incidence, premature luteinization (PL) and pregnancy rate per cycle. RESULTS: Premature LH rise incidence was 2.6% (3 cycles) and PL 6% (7 cycles). Group 1 didn't present cycles with LH rise or PL, groups 2 and 3 presented LH rise in 3.1% and 1.8% and PL in 12.5% and 5.4% respectively. Pregnancy rate with GnRHant was 16.4% (95% IC 8.1-28.1) vs. 7.2% (95% le 2.0-17.5%) without GnRHant (group 3) (p = 0.16): groups 1 and 2 represented a pregnancy rate of 20.6% (95% IC 7.9-39.7) and 12.5% (95% IC 3.5-28.9%) respectively (p = 0.49). Mature follicles number reached meaning difference between all groups (p = 0.04) specially between groups 1 and 2 (p = 0.02). CONCLUSIONS: A trend to elevate pregnancy rates was observed with GnRHant specially with when it was started when leading follicle reached 14 mm (p > 0.05). Starting GnRHant with 16 mm was not totally usefully to prevent PL.

Patient evaluation of the use of follitropin alfa in a prefilled ready-to-use injection pen in assisted reproductive technology: an observational study.

BACKGROUND: Self-administration of recombinant human follicle-stimulating hormone (r-hFSH) can be performed using injection pen devices by women undergoing assisted reproductive technology procedures. The objective of this study was to explore the use of the prefilled follitropin alfa pen in routine assisted reproductive technology procedures in Germany. METHODS: This prospective, observational study was conducted across 43 German IVF centres over a period of 1.75 years. Patients who had used the prefilled follitropin alfa pen in the current or a previous cycle of controlled ovarian stimulation completed a questionnaire to assess their opinions of the device. RESULTS: A total of 5328 patients were included in the study. Of these, 2888 reported that they had previous experience of daily FSH injections. Significantly more patients reported that less training was required to use the prefilled follitropin alfa pen than a syringe and lyophilized powder (1997/3081 [64.8%]; p < 0.001 'less' versus 'more' training). Significantly more patients rated the prefilled follitropin alfa pen as easier in terms of use (2321/3206, 72.4%; p < 0.001 'much more easy' versus 'less easy') and daily injection (2384/3262, 73.1%; p < 0.001 'much more easy' versus 'less easy') than existing injection methods. Approximately one third of respondents rated the prefilled follitropin alfa pen as easier to use than the follitropin beta pen with reloadable cartridges. The majority (3378/4024, 83.9%) of patients had a general preference for the prefilled follitropin alfa pen over other injection methods. CONCLUSIONS: In this questionnaire-based survey, routine use of the prefilled follitropin alfa pen was well accepted and associated with favourable patient perceptions. Users of the pen found it easier to initially learn how to use, and subsequently use, than other injection methods. In general, the prefilled follitropin alfa pen was the preferred method for self-administration of gonadotrophins. Together with previous findings, the results here indicate a high level of patient satisfaction among users of the prefilled follitropin alfa pen for daily self-administration of r-hFSH.

Factors related to successful ovulation induction in patients with WHO group II anovulatory infertility.

To identify baseline characteristics related to successful ovulation induction, data were analysed from oligo- or anovulatory patients undergoing their first cycle of human recombinant FSH (r-hFSH; follitropin alfa) in a chronic low-dose (75 IU starting dose), step-up protocol in two clinical trials (n=446). Patients were grouped according to response: group A, ovulated within 14 days (75 IU follitropin alfa); group B, ovulated after 14 days (>75 IU follitropin alfa); group C, not administered human chorionic gonadotrophin (HCG) because of poor response; group D, cycle cancelled due to over-response (HCG not administered); group E, spontaneous ovulation prior to obtaining criteria for administration of HCG. Mean body mass index (BMI) of group A (25.0 kg/m(2)) was significantly lower than groups B (27.1 kg/m(2), P<0.001) or C (28.2 kg/m(2), P<0.0001), but similar to group D (24.3 kg/m(2)). Mean antral follicle count (AFC) of group A was also significantly lower than group C (18.3 versus 22.7; P=0.018), but not significantly different from groups B (21.5) or D (19.5); group E had the highest mean AFC (35.7). Comparatively low BMI, low AFC and higher (although still within the normal range) FSH concentration at baseline were associated with successful ovulation induction in infertile women undergoing a chronic low-dose, step-up stimulation protocol.

Safety and efficacy of mixing cetrorelix with follitropin alfa: a randomized study.

OBJECTIVE: To assess the safety and efficacy of mixing cetrorelix with follitropin alfa (rFSH) in assisted reproductive technology. DESIGN: Prospective, randomized study. SETTING: An IVF center in a teaching hospital. PATIENT(S): One hundred forty patients undergoing intracytoplasmic sperm injection were randomized into mixed (M) or separate (S) injection groups. INTERVENTION(S): In the M group, rFSH and cetrorelix were mixed immediately before administration, whereas in the S group, rFSH and cetrorelix were administered separately. MAIN OUTCOME MEASURE(S): The primary efficacy end point was the incidence of premature LH surge. The secondary efficacy endpoints included estradiol levels on the day of hCG injection, numbers of oocytes obtained, implantation, and ongoing pregnancy rates. The safety endpoints included ovarian hyperstimulation syndrome, and adverse events related to injections including local tolerability. RESULT(S): Excluding eight patients who dropped out of the study, there were 66 patients in each group for analysis. Patients in the M group received significantly fewer injections than patients in the S group (9.1 vs. 13.9). Other outcome parameters, including incidences of premature LH surge, numbers of oocytes retrieved, fertilization, implantation, and ongoing pregnancy rates were similar between the two groups. CONCLUSION(S): Cetrorelix and rFSH can be mixed together without compromising their reported safety and efficacy. This observation is in line with the reported safety and efficacy profile of the products listed in their current package inserts.

Outcomes of new quality standards of follitropin alfa on ovarian stimulation: meta-analysis of previous studies.

BACKGROUND: Human follicle-stimulating hormone (hFSH; follitropin alfa) can be employed therapeutically to induce ovarian follicular development in assisted reproduction treatments. Current recombinant hFSH (r-hFSH) preparations available for clinical use are labeled either in terms of the bioactivity expressed in international units (IU) or in mass (microg). Several clinical trials have tried to assess the clinical implications of the physicochemical improvements in the dosing of follitropin alfa filled by mass (FbM). The aim of this study was to perform a meta-analysis of previous studies in order to assess the efficacy and safety of ovarian stimulation using follitropin alfa FbM compared with follitropin alfa filled by international units (FbIU). METHODS: A literature search was carried out in scientific databases to find published articles and abstracts comparing both hormone preparations. A fixed effects model meta-analysis was performed. The variables studied include the average dose (IU), days of treatment, estradiol peak, follicles >14 mm, number of extracted oocytes, number of embryos obtained, number of cases of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancies. RESULTS: A total of six studies met the stated criteria and were included in the meta-analysis. In these studies, the average r-hFSH dose per patient was 230.29 IU less with administration of follitropin alfa FbM compared with FbIU, and the number of days of treatment was reduced by 0.48. In addition, a significantly greater number of oocytes (0.84) were extracted, more embryos (0.88) were obtained, and a higher peak level of estradiol (613.08 pmol/L) was achieved in the patients undergoing ovarian stimulation with follitropin alfa FbM. However, no statistically significant differences were observed in the number of follicles >14 mm, clinical pregnancies, or OHSS cases. CONCLUSION: Follitropin alfa FbM, a technologically modified formulation of r-hFSH, is as safe as follitropin alfa FbIU but requires a smaller dose over a shorter period to produce more oocytes and final embryos.

The effect of endometrial thickness on in vitro fertilization (IVF)-embryo transfer/intracytoplasmic sperm injection (ICSI) outcome.

The value of measuring the endometrial thickness and studying the endometrial receptivity in the context of assisted conception remains a contentious issue. A prospective analysis was carried out to determine the effect of endometrial thickness on IVF - embryo transfer/ICSI outcome in dedicated Assisted Reproductive Technology (ART) units in Abuja and Rivers State, Nigeria. Two hundred and fifty one patients who met the inclusion criteria were analysed. They were grouped on the basis of endometrial thickness into 3 groups; <7 mm, 7 - 14 mm and >14 mm. The main outcome measure was clinical pregnancy. There were significantly more pregnancies in the 7 - 14 mm endometrial thickness group compared to the <7 mm and >14 mm groups, p=0.004 and p<0.0001 respectively. The findings suggest that following IVF/ICSI, significantly more pregnancies occurred when the endometrial thickness was between 7 and 14 mm.

A prospective comparison of in vitro fertilization (IVF) outcome following controlled ovarian hyperstimulation (COH) regimens using follitropin alpha exclusively or with the addition of low dose human chorionic gonadotropin (hCG) and ganirelix.

PURPOSE: To determine if the addition of luteinizing hormone (LH) activity to a controlled ovarian hyperstimulation regimen for purposes of in vitro fertilization adds any additional benefit to the exclusive use of recombinant (r) FSH in antagonist protocols. METHODS: Women with normal endogenous gonadotropin levels were randomly assigned to receive either follitropin alpha exclusively or have the addition of 25 IU human chorionic gonadotropin (hCG) daily. Ganirelix was used when a 14 mm follicle was attained. The data would be analyzed after 70 women were selected for the study and divided into two groups. RESULTS: There were 22 women in each group who proceeded with embryo transfer (some purposely cryopreserved all embryos because of risk of ovarian hyperstimulation syndrome). There were no trends for differences in clinical or delivered pregnancy rates or implantation rates. CONCLUSIONS: There does not appear to be any clinical advantage of adding exogenous LH activity to the drug regimen for stimulation of multiple follicles for purposes of in vitro fertilization when using follitropin alpha in an antagonist protocol.

Patient and nurse evaluation of recombinant human follicle-stimulating hormone administration methods: comparison of two follitropin injection pens.

OBJECTIVE: Ovarian stimulation by injection of gonadotrophins is an essential part of assisted reproductive technology (ART) protocols. Two studies (a German pilot study and an Australian study) aimed to assess and compare the ease-of-use, safety and efficacy of two follitropin injection pens. METHODS: Patient satisfaction (questionnaire) and safety were assessed in patients undergoing ART at a German centre for in vitro fertilisation (IVF), randomised either to the follitropin alfa pen or to the follitropin beta pen. Patient satisfaction (questionnaire) was assessed in patients undergoing ART at an Australian IVF centre, using the follitropin alfa pen, and previous experience with the follitropin beta pen was compared. The experience of IVF nurses with both pens was assessed using a similar questionnaire. Statistical significance was not determined in either study. RESULTS: In the German study (n = 31), patients favored the follitropin alfa pen over the follitropin beta pen because they found preparation faster, were more confident of accurate dosing and had to make fewer dose adjustments. Treatments delivered by both pens were well tolerated; eight adverse events (AEs) occurred, two AEs (including one case of ovarian hyperstimulation syndrome, OHSS) in two patients using the follitropin alfa pen and six AEs (including three cases of OHSS, one of which was serious) in six patients using the follitropin beta pen. Patients (n = 140) and nurses (n = 11) in the Australian study scored the follitropin alfa pen highly and patients favored it over the follitropin beta pen; the risk of OHSS was also considered greater in the follitropin beta pen group, with nearly a twofold higher rate of cycle cancellation due to OHSS risk compared with the follitropin alfa pen group. CONCLUSIONS: Taken together, results from these two small studies suggest that the follitropin alfa pen was effective, well tolerated, and patient and nurse acceptance appeared to be higher for the follitropin alfa pen versus the follitropin beta pen, which may benefit compliance, leading to improved outcomes.

A comparison of the efficacy, tolerability, and convenience of two formulations of follitropin-alpha in Iranian woman undergoing intracytoplasmic sperm injection cycles.

OBJECTIVE: To compare the efficacy, tolerability, and convenience of two formulations of the follitropin-alpha (Gonal-f) pen device versus the conventional form in Iranian women undergoing ovarian stimulation for intracytoplasmic sperm injection. DESIGN: Randomized, single-center trial, parallel-group, single blind. SETTING: Tertiary referral center, University Hospital. PATIENT(S): A total of 100 patients undergoing intracytoplasmic sperm injection. INTERVENTION(S): After down-regulation with busereline acetate, patients were randomized to receive the pen device or the conventional syringe of follitropin-alpha. A computer-generated randomization list was used to allocate the patients to one of these two groups. MAIN OUTCOME MEASURE(S): The primary outcomes were patients' satisfaction, convenience, occurrence of local tolerance symptoms, and pain. Total dose of follitropin-alpha, duration of follitropin-alpha treatment, number of oocyte retrieved, number of viable embryos, and clinical pregnancies were secondary outcome measures. Data collection was performed by means of a questionnaire designed for the purpose of this study. The pain scored according to the Visual Analogue Scale. RESULT(S): Self-administration and patients' satisfaction were significantly higher in the pen device group than the conventional syringe group. Local reactions at injection sites and pain were significantly higher in the conventional syringe group than in the pen device group. There were no statistically differences in secondary outcome measures and convenience between two groups. CONCLUSION(S): Among the Iranian patients that we studied, the pen device of Gonal-f is safe, convenient, and less painful, with more patients' satisfaction than the conventional syringe form, but both forms have equal efficacy in intracytoplasmic sperm injection cycles.

[Ovulation induction in high risk IVF patients: GnRH-agonist, diminished dose of urinary or recombinant chorion gonadotropin].

In high risk IVF patients the ovulation triggering was done with agonist (0.2 mg), 1.gr., Pregnyl 5000 IE, 2. and 4.gr., Ovitrelle 0.250 mg, 3.gr., and Pregnyl 10000 IE in the fifth--non-risk group. The protocol of the first and fourth group included antagonist, the second and third group was with short and the fifth group with long agonist protocol. There was no grave OHSS in the first group, one case in each second, third and fourth group and 4 cases in the fifth group, as a whole 7 patients (3.3%). In all of them an abdominal drainage lasting 4 to 30 days was performed and all pregnancies were preserved. The average success rate was 50%, 71.4% in the fourth and 43.1% in the fifth group. A protocol with antagonist and ovulation triggering with agonist or reduced dose ChG in order to diminish OHSS in high risk IVF patients is recommended.

A comparison between follitropin alpha filled by mass and follitropin alpha filled by bioassay in the same egg donors.

This study assessed the ovarian stimulation characteristics of recombinant follitropin alpha filled by mass (rFSH-fbm) versus recombinant follitropin alpha filled by conventional bioassay (rFSH-bio) in the same egg donor patients. Eleven egg donors, who had two ovarian stimulation cycles for oocyte retrieval (total of 23 cycles), one with rFSH-bio (Gonal-f Multidose) and the second one with rFSH-fbm (Gonal-f RFF), were evaluated. The protocol of ovarian stimulation was exactly the same in both cycles, consisting of GnRH suppression (luteal phase) followed by exclusive stimulation with rFSH. Despite no differences in the number of days of rFSH treatment and in the total dosage of rFSH administered, the number of follicles >14 mm and the number of oocytes retrieved were significantly higher in the rFSH-fbm group (P = 0.01 and 0.04 respectively). The mean oestradiol peak values showed a trend in favour of rFSH-fbm (3123 versus 2405 pg/ml respectively). These results suggest that the consistency in dosing provided by follitropin alpha filled by mass as opposed to follitropin alpha filled by bioassay offers added value for the ovarian stimulation of oocyte donor patients.