Table of Contents

Stakeholder Insight: Infertility - Undifferentiated drugs force need to strengthen prescriber and payer relationship - This report is based on a survey of 180 physicians across the seven major markets covering key issues in infertility; including epidemiology, presentation, diagnosis and treatment trends, prescribing influences, and brand assessments.

Product Code: dmhc2418

Publication Date: 17-Dec-2008

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Overview

Introduction

Over 11.5 million women suffer from infertility in the seven major markets. Although prevalence rates are stable, the trend towards later parenthood is inducing an increasing demand for infertility treatments. As cost of therapy is the major barrier access, the raise in demand puts increased pressure on healthcare payers to reimburse these treatments across the seven major markets.

Scope

· Patient segmentation including detailed etiology of female and male infertility.

· Analysis of presentation, diagnosis, and treatment trends as well patient referral pathways in each of the major regions.

· In vitro fertilization treatment trends split by therapy protocol type, treatment regimen and drug class prescribed. Detailed IVF treatment outcomes.

· Prescriber scoring of key drug brands on factors including efficacy, side effects, dosing flexibility, formulations, patient compliance, and cost.

Highlights

Prescribers perceive available IVF drugs are largely undifferentiated from each other. This allows physicians to prescribe according to personal preference and convenience, which means companies need to build strong relationships with physicians to increase brand loyalty.

Companies with urinary products need to strongly compete on a lower cost profile by lobbing with IVF payers and need to guarantee supply reliability. In Japan, where physicians prescribe 56% of follicle stimulating hormone and 80% of human chorionic gonadotropins in their urinary forms there is a clear opportunity for urinary companies.

The low scoring of Pergoveris (follitropin-alpha and luveris-alpha, Merck Serono) and Org36286 (corifollitropin-alpha, Organon) by survey respondents suggests that there is limited commercial potential for straightforward reformulations of existing drugs. There is a greater need for oral formulations.

Reasons to Purchase

· Target physicians more effectively through an understanding of prescribing behavior and its influences.

· Validate new product forecasting based on diagnosis and treatment rates, and the likely rate of uptake for new products.

· Benchmark brand awareness and perceptions surrounding product positioning in order to formulate competitive lifecycle management strategies.

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ABOUT DATAMONITOR HEALTHCARE	2
About the Genitourinary pharmaceutical analysis team	2
CHAPTER 1 EXECUTIVE SUMMARY	3
Scope of the analysis	3
Datamonitor insight into the Infertility market	3
Contributing experts	5
Related reports	5
CHAPTER 2 INTRODUCTION AND SCOPE	7
Coverage of the Stakeholder Insight Survey	7
Epidemiology and patient segmentation	9
Diagnosis, presentation and referral options	9
Treatment options and trends	9
Key prescribing influences and brand assessment	9
Improving treatment outcomes	9
Assumptions and caveats	10
Future trends	10
CHAPTER 3 COUNTRY TREATMENT TREES	11
Introduction to treatment trees	11
Assumptions and caveats	12
US	13
Japan	14
France	15
Germany	16
Italy	17
Spain	18
UK	19
CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION	20
Disease definition	21
Overview of conception	21
The causes of infertility	23
Female infertility	24
Hormonal imbalances	26
Polycystic ovaries syndrome	27
Endometriosis	29
Pelvic inflammation disease	30
Uterine fibroids	30
Male infertility	31
Sperm disorders	32
Obstructive azoospermia	33
Varicocele	33
Medication side effects	33
Hormonal imbalances	33
Joint infertility	33
Unexplained infertility	34
Infertility prevalence	34
There are over 11 million infertile women across the seven major markets	34
US	36
Japan	37
France	37
Germany	37
Italy	37
Spain	38
UK	38
Trends in epidemiology	38
Infertility prevalence rates have been stable over the years	38
Alternative infertility candidates expands market potential	39
Demand for infertility treatment is expected to grow although female prevalence is stable	40
CHAPTER 5 PRESENTATION, DIAGNOSIS, AND REFERRAL OPTIONS	43
Presentation	44
Diagnosis	45
Diagnostic tests	46
Male tests	46
Female tests:	46
Diagnostic unmet need	47
Over 50% of female infertility cases are diagnosed between the ages of 31 and 40 years	48
Female age of diagnosis affects treatment options	49
Over 30% of male infertility is diagnosed over 40 years of age	49
Referral patterns	50
US	51
Europe	52
On average, it takes a patient 11 months to be referred to an infertility specialist in the seven major markets	53
CHAPTER 6 TREATMENT OPTIONS AND TRENDS	55
Introduction	56
Treatment rates	56
Pharmacological versus non-pharmacological	56
In vitro fertilization treatment rates are low due to cost, stress, and poor success rates	57
Assisted reproduction techniques	60
Ovulation induction	61
Intrauterine insemination	62
Assisted hatching	63
Overview of in vitro fertilization	64
Long or downregulation protocol	66
Short or flare up protocol	66
Other protocols	67
Mixed	67
Mild stimulation	67
Natural	69
In vitro fertilization therapy stages	69
Ovarian stimulation	69
Egg retrieval	70
Embryo retransfer	70
Trends in in vitro fertilization	71
Long in vitro fertilization protocols are the most common across the seven major markets	71
On average a woman can receive three to four in vitro fertilization cycles per year	73
Cryopreservation	75
Cryopreservation will increase as the freezing techniques improve and become safer for the embryo	75
Overview of available drug classes	77
Follicle stimulating hormone	78
Human menopausal gonadotropins	83
Luteinizing hormone	84
Human chorionic gonadotropin	85
Gonadotropin releasing hormones	87
Controversies surrounding drug classes	92
Human menopausal gonadotropin versus follicle stimulating hormone - no evidence of significant difference in clinical outcomes	92
Recombinant versus urinary products - physicians choose recombinants based on perceived superior efficacy and safety	95
Treatment guidelines	97
National Institute for Health and Clinical Excellence	97
American Society for Reproductive Medicine.	97
Japan Association of Obstetricians and Gynecologists	98
European Society for Human Reproduction and Embryology	98
In vitro fertilization laws and regulations	98
Trends in pharmacological treatment	101
Human chorionic gonadotropins and gonadotropin releasing hormone agonists are the most widely used drug classes	101
US physicians prescribe fewer drug combinations than in other markets	102
Many different treatment regimens are prescribed	103
Drug regimens rarely change between first and second cycles	111
Monotherapies are seldom used in Japan and the five EU countries	112
Gonadotropin releasing hormone antagonists are not prescribed in the most common treatment regimens	112
Unlike other countries, in Germany no drug regimen is preferred to another	113
Future trends in assisted reproduction	113
In vitro maturation is limited by safety concerns	113
Current data show that in vitro maturation yields similar pregnancy rates as in vitro fertilization	114
In vitro maturation and fertility preservation	114
Is in vitro maturation the future?	115
Reproductive tourism	115
CHAPTER 7 PRESCRIBING INFLUENCES AND BRAND ASSESSMENT	117
Factors influencing physician decision making	118
The cost of drugs remains one of the most important drug attributes in most countries.	119
Physician perception of key brands	120
Total drug scores per drug per country	122
Interpreting a brand map	124
In vitro fertilization drugs are all very similar in terms of physician perception	124
Follicle stimulating hormones	125
Human menopausal gonadotropins	129
Physicians perception shows that no drug is clearly defined by any one attribute	131
Gonadotropin releasing hormone analogs	132
Pipeline drugs	136
CHAPTER 8 IMPROVING TREATMENT OUTCOMES	139
Treatment outcomes	140
Up to half of women receiving in vitro fertilization treatment achieve pregnancy	140
Age greatly affects in vitro fertilization outcomes	141
Lifestyle, such as smoking and stress, adversely impacts fertility	143
In vitro fertilization outcomes in the US and in the UK	143
The majority of patients will achieve pregnancy within completion of the third in vitro fertilization cycle	144
Lack of finances is not the only reason for interruption of in vitro fertilization treatment	146
Pregnancy then single live births are the main goals of in vitro fertilization	148
Embryo quality is key to in vitro fertilization success	150
Unmet needs	151
Reduction in patient payments will increase access and expand market	152
Price and reimbursement schemes limit access to in vitro fertilization	153
Development of novel drug targets for in vitro fertilization treatment	157
Improvement of drug administration route is the key successful factor for a new product entering the market	158
BIBLIOGRAPHY	159
Journal papers	159
Websites	166
Other	169
APPENDIX A - PHYSICIAN SAMPLE	170
Physician research methodology	170
Physician sample breakdown	170
US	170
Japan	171
France	171
Germany	172
Italy	172
Spain	173
UK	173
Contributing experts	174
APPENDIX B - SCREENER AND SURVEY QUESTIONNAIRE	175
Screener questionnaire	175
Survey questionnaire	175
Section 1 - Presentation and Diagnosis	175
Section 2 - Treatment Cycles: IVF/IVF/ICSI	177
Section 3 - Treatment Outcomes	182
Section 4 - Product Profiles	184
Section 5 - Demographics	185
APPENDIX C - ABOUT DATAMONITOR	187
About Datamonitor	187
About Datamonitor Healthcare	187
About the Genitourinary analysis team	188
Disclaimer	190
List of Tables
Table 1: Causes of female infertility, 2008	25
Table 2: World Health Organization classifications of polycystic ovarian syndrome	27
Table 3: Causes of male infertility	31
Table 4: Prevalence of female infertility in the seven major markets, 2008	35
Table 5: Summary of studies that determine the prevalence rate of female infertility in the seven major markets, 2008	36
Table 6: In vitro fertilization treatment rates and patient and cycle numbers across the seven major markets, 2008	58
Table 7: Number of clinics and in vitro fertilization cycles in the five EU countries, 1998-2004	59
Table 8: Number of infertility clinics per patient in the seven major markets, 2000	59
Table 9: Branded follicle stimulating hormones (FSH) available in the seven major markets, 2008	79
Table 10: Comparison of costs of recombinant versus urinary infertility products in the US, 2007	81
Table 11: Branded human menopausal gonadotropins (hMG) available in the seven major markets, 2008	83
Table 12: Branded human chorionic gonadotropins (hCG) available in the seven major markets, 2008	85
Table 13: Branded gonadotropin releasing hormones (GnRH) available in the seven major markets, 2008	88
Table 14: Summary of key studies comparing human menopausal gonadotropins (hMG) to recombinant follicle stimulating hormone (FSH)	94
Table 15: Country-specific in vitro fertilization (IVF) practices in the seven major markets, 2008	99
Table 16: Summary of infertility drug availability in the seven major markets, 2008	120
Table 17: Number and percentage of physicians who were able to rate each infertility drug, 2008	121
Table 18: Total score (out of 100) for each infertility drug in the seven major markets, 2008	122
Table 19: In vitro fertilization outcomes in the US for fresh non-donor cycles, 2005	143
Table 20: In vitro fertilization outcomes with and without intracytoplasmic injection for fresh non-donor cycles in the UK, 2006	144
Table 21: Summary of assisted reproduction techniques coverage in the seven major markets, 2008	153
Table 22: US physician sample breakdown, 2008	170
Table 23: Japan physician sample breakdown, 2008	171
Table 24: France physician sample breakdown, 2008	171
Table 25: Germany physician sample breakdown, 2008	172
Table 26: Italy physician sample breakdown, 2008	172
Table 27: Spain physician sample breakdown, 2008	173
Table 28: UK physician sample breakdown, 2008	173
List of Figures
Figure 1: Diagrammatic overview of the coverage of the Stakeholder Insight: Infertility survey, 2008	8
Figure 2: US infertility treatment tree, 2008	13
Figure 3: Japan infertility treatment tree, 2008	14
Figure 4: France infertility treatment tree, 2008	15
Figure 5: Germany infertility treatment tree, 2008	16
Figure 6: Italy infertility treatment tree, 2008	17
Figure 7: Spain infertility treatment tree, 2008	18
Figure 8: UK infertility treatment tree, 2008	19
Figure 9: Overview of the menstrual cycle	22
Figure 10: Regulation of follicle development by the hypothalamus-pituitary gland-ovary axis, 2008	23
Figure 11: The cause of infertility by gender across the seven major markets, 2008	24
Figure 12: Female infertility etiology breakdown in the seven major markets, 2008	25
Figure 13: Summary of possible treatments for female infertility ,2008	26
Figure 14: Male infertility etiology breakdown in the seven major markets, 2008	32
Figure 15: Percentage of women undergoing IVF who are single or in a same sex relationship in the seven major markets, 2008	39
Figure 16: Number of in vitro fertilization cycles in the five EU countries, 1998-2004	40
Figure 17: Number of in vitro fertilization clinics in the five EU countries, 1998-2004	41
Figure 18: Decline of fertility rates in the seven major markets, 1970-2002	42
Figure 19: Percentage of potentially infertile population presenting for treatment in the seven major markets, 2008	44
Figure 20: Infertility diagnosis rate in the seven major markets, 2008	45
Figure 21: Breakdown of age at diagnosis of female infertility in the seven major markets, 2008	48
Figure 22: Breakdown of age at male infertility diagnosis in the seven major markets, 2008	49
Figure 23: Consultation breakdown for infertility patients in the seven major markets, 2008	50
Figure 24: US referral pathway for infertility patients, 2008	51
Figure 25: Referral pathway in major five EU markets for infertility patients, 2008	52
Figure 26: Duration of referral pathways for infertility patients in the seven major markets, 2008	53
Figure 27: Breakdown of pharmacological and non pharmacological infertility treatment in the seven major markets, 2008	57
Figure 28: Treatment algorithm for infertility in the seven major markets, 2008	60
Figure 29: Assisted reproduction technique treatment options, 2008	61
Figure 30: Intrauterine insemination	62
Figure 31: Assisted hatching for in vitro fertilization treatment patients	64
Figure 32: In vitro fertilization (IVF) treatment pathway, 2008	65
Figure 33: Breakdown of in vitro fertilization (IVF) protocol types in the seven major markets, 2008	72
Figure 34: Comparison of in vitro fertilization (IVF) protocol types in the first and second treatment cycles in the total seven major markets, 2008	73
Figure 35: Average number of in vitro fertilization (IVF) cycles initiated per patient per year across the seven major markets, 2008	74
Figure 36: Overview of embryo transfer trends in in vitro fertilization (IVF) treatment across the seven major markets, 2008	77
Figure 37: Typical treatment procedure timeline during one in vitro fertilization cycle, 2008	78
Figure 38: Breakdown of urinary versus recombinant follicle stimulating hormone (FSH) use in the seven major markets, 2008	82
Figure 39: Breakdown of urinary versus recombinant human chorionic gonadotropin (hCG) use in the seven major markets, 2008	87
Figure 40: Breakdown of gonadotropin releasing hormone agonists and antagonists use across the seven major markets, 2008	90
Figure 41: Physician reasons for prescribing a gonadotropin releasing hormone (GnRH) antagonist rather than an agonist in the seven major markets, 2008	91
Figure 42: Reasons for prescribing a recombinant rather than a urinary product for in vitro fertilization (IVF) treatment in the seven major markets, 2008	95
Figure 43: Percentage of patients receiving drug classes used for in vitro fertilization (IVF) treatment in the seven major markets, 2008	102
Figure 44: Percentage of patients receiving drug classes used for in vitro fertilization (IVF) treatment by country, 2008	103
Figure 45: Percentage of patients receiving first and second treatment cycle regimens for in vitro fertilization (IVF) patients in the US, 2008	105
Figure 46: Percentage of patients receiving first and second treatment cycle regimens for in vitro fertilization (IVF) patients in Japan, 2008	106
Figure 47: Percentage of patients receiving first and second treatment cycle regimens for in vitro fertilization (IVF) patients in France, 2008	107
Figure 48: Percentage of patients receiving first and second treatment cycle regimens for in vitro fertilization (IVF) patients in Germany, 2008	108
Figure 49: Percentage of patients receiving first and second treatment cycle regimens for in vitro fertilization (IVF) patients in Italy, 2008	109
Figure 50: Percentage of patients receiving first and second treatment cycle regimens for in vitro fertilization (IVF) patients in Spain, 2008	110
Figure 51: Percentage of patients receiving first and second treatment cycle regimens for in vitro fertilization (IVF) patients in the UK, 2008	111
Figure 52: Number of points allocated to each infertility drug attribute to indicate its relative importance in the seven major markets, 2008	118
Figure 53: Number of points allocated to each infertility drug attribute, excluding efficacy and side effects, to indicate its relative importance in the seven major markets, 2008	119
Figure 54: Brand map of the scores of the individual products used in in vitro fertilization (IVF) in relation to each other, 2008	125
Figure 55: Number of points allocated to each follicle stimulating hormone (FSH) for all factors in the seven major markets, 2008	126
Figure 56: Percentage of patients receiving follicle stimulating hormones (FSH) split by brand in the seven major markets, 2008	127
Figure 57: Number of points allocated to each human menopausal gonadotropin (hMG) for all factors in the seven major markets, 2008	129
Figure 58: Percentage of patients receiving human menopausal gonadotropins (hMG) by brand in the seven major markets, 2008	130
Figure 59: Brand map of follicle stimulating hormones (FSH) and human menopausal gonadotropins (hMG), 2008	131
Figure 60: Number of points allocated to each follicle stimulating hormone (FSH) and human menopausal gonadotropin (hMG) for all factors in the seven major markets, 2008	132
Figure 61: Number of points allocated to each gonadotropin releasing hormone (GnRH) analog on all factors in the seven major markets, 2008	133
Figure 62: Percentage of patients receiving gonadotropin releasing hormone (GnRH) antagonists by brand in the seven major markets, 2008	134
Figure 63: Percentage of patients receiving gonadotropin releasing hormone (GnRH) agonists by brand in the seven major markets, 2008, 2008	135
Figure 64: Number of points allocated to Pergoveris in the seven major markets, 2008	136
Figure 65: Number of points allocated to Org-36286 in the seven major markets, 2008	138
Figure 66: In vitro fertilization (IVF) and in vitro fertilization/ intracytoplasmic injection (IVF/ICSI) treatment outcomes in the seven major markets, 2008	140
Figure 67: Change of first time mother's age in the seven major markets, 2006	142
Figure 68: Number of in vitro fertilization (IVF) cycles completed before achieving pregnancy in the seven major markets, 2008	145
Figure 69: Number of in vitro fertilization (IVF) treatment cycles completed before discontinuation for any reason in the seven major markets, 2008	146
Figure 70: Reasons for interruption in vitro fertilization (IVF) treatment in the seven major markets, 2008	147
Figure 71: Pregnancy outcomes following in vitro fertilization (IVF) treatment in the seven major markets, 2008	148
Figure 72: Unmet need in in vitro fertilization (IVF) treatment according to interviewed key opinion leaders, 2008	151
Figure 73: Reimbursement coverage of in vitro fertilization (IVF) or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in the seven major markets, 2008	154

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