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Infertility, In Vitro Fertilization (IVF) and Genetic Testing Susan Sarajari, M.D., Ph.D.

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Presentation on theme: "Infertility, In Vitro Fertilization (IVF) and Genetic Testing Susan Sarajari, M.D., Ph.D."— Presentation transcript:

1 Infertility, In Vitro Fertilization (IVF) and Genetic Testing Susan Sarajari, M.D., Ph.D.

2 History of Infertility First written document dealing with infertility may be found in the Kahoun papyrus (oldest Egyptian medical text), dated to BC First written document dealing with infertility may be found in the Kahoun papyrus (oldest Egyptian medical text), dated to BC The early attribution of infertility to women persisted for centuries and was often considered divine punishment The early attribution of infertility to women persisted for centuries and was often considered divine punishment The only solution to infertility was prayer – to Egyptian Isis, Phoenician Astarte, Greek Aphrodite, or Roman Venus The only solution to infertility was prayer – to Egyptian Isis, Phoenician Astarte, Greek Aphrodite, or Roman Venus The role of the human male in reproduction was not understood in past civilizations and is still veiled in mystery for many of the primitive tribes The role of the human male in reproduction was not understood in past civilizations and is still veiled in mystery for many of the primitive tribes

3 Overview of Infertility Definition: 1 year of well-timed, unprotected intercourse without a pregnancy Definition: 1 year of well-timed, unprotected intercourse without a pregnancy 10-15% of population is infertile 10-15% of population is infertile % of couples have unexplained infertility (work-up is negative) % of couples have unexplained infertility (work-up is negative)

4 Causes of Infertility

5 Female Reproductive Organs

6 FSH (+) FSH=Follicle Stimulating Hormone Physiology E2 (-) E2=Estradiol Developing follicle

7 Ovary - Female Age Women are born with their lifetime egg supply Women are born with their lifetime egg supply 4 million at 20 weeks gestation 4 million at 20 weeks gestation 400,000 at birth 400,000 at birth 100,000 eggs left at time of puberty 100,000 eggs left at time of puberty Fertility initially declines at age 27 Fertility initially declines at age 27 Significant decline at age Significant decline at age Rare pregnancies after age 44 Rare pregnancies after age 44

8 Causes of Female Infertility Ovary Ovary Tubes Tubes Uterus Uterus Cervix Cervix Hormones Hormones Chromosomes Chromosomes

9 Causes of Female Infertility - Ovary Age Age Problems with ovulation Problems with ovulation Premature ovarian failure Premature ovarian failure

10 Percentage of Married Women Who are Infertile From 3 national U.S. surveys Age (years) Infertile Menken et al, Science 1989;23:1389

11 Fertility and age: natural populations Marital fertility rates in natural populations (no contraception) as a function of age of wife Science 1986;23:1389

12 FSH (+) FSH=Follicle Stimulating Hormone Effects of Aging on the Ovary E2 (-) E2=Estradiol

13 Why does fertility decline with increasing maternal age? Decline in the number of eggs Decline in the number of eggs Every month there is loss of a group of eggs Every month there is loss of a group of eggs Decline in the quality of eggs Decline in the quality of eggs As the egg ages, errors in the dividing embryo increase As the egg ages, errors in the dividing embryo increase These errors may result in aneuploidy (an incorrect number of chromosomes) These errors may result in aneuploidy (an incorrect number of chromosomes)

14 Prevalence of genetically abnormal oocytes in infertile women % Abnormal

15 Ovary - Causes of Anovulation Hormone imbalance Hormone imbalance Obesity Obesity Anorexia Anorexia Significant stress Significant stress Patients display: Patients display: Irregular menstrual cycles Irregular menstrual cycles Skipped cycles Skipped cycles Minimal or absent premenstrual symptoms Minimal or absent premenstrual symptoms

16 Ovary – Premature Ovarian Failure Menopause prior to age 40 Menopause prior to age 40 Decreased Estrogen Decreased Estrogen Increased FSH Increased FSH Causes Causes Autoimmune Autoimmune Genetic Genetic Idiopathic Idiopathic 1-2% pregnancy rate 1-2% pregnancy rate

17 Causes of Female Infertility – Fallopian Tubes Infection (chlamydia) Infection (chlamydia) Endometriosis Endometriosis Tubal ligation (female sterilization) Tubal ligation (female sterilization)

18 Open Tubes

19 Blocked Tubes

20 Female Infertility - Uterus Uterus Uterus Fibroids Fibroids Polyps Polyps

21 Female Infertility Uterine muscle tumor Benign (>95%) 25-30% of women

22 Normal Shape of Uterus

23 Fibroid Uterus

24 Female Infertility - Uterus Mullerian defects (congenital) Mullerian defects (congenital) Absent uterus Absent uterus Bicornuate/septate Bicornuate/septate

25 Mullerian Defect

26 Treatment with Hysteroscopy

27 Treatment with Laparoscopy

28 Female Infertility - Cervix Cervix Cervix Post-surgical Post-surgical Stenosis Stenosis Mucus changes Mucus changes

29 Female Infertility - Hormones Endocrine abnormality (hormones) Endocrine abnormality (hormones) Thyroid Thyroid Prolactin Prolactin Polycystic ovary syndrome (PCOS) Polycystic ovary syndrome (PCOS) Estrogen, insulin Estrogen, insulin Hypothalamic hypogonadism Hypothalamic hypogonadism Stress Stress Exercise (athlete) Exercise (athlete)

30 Other Causes of Female Infertility Chromosome abnormalities Chromosome abnormalities Turners syndrome (XO) Turners syndrome (XO) Androgen Insensitivity (XY) Androgen Insensitivity (XY) Male pseudohermaphrodite Male pseudohermaphrodite Female phenotype Female phenotype Blind vaginal canal Blind vaginal canal Inguinal hernia (50%) Inguinal hernia (50%)

31 Sperm Are Also Required!!

32 Male Reproductive Organs

33 Causes of Male Infertility Abnormality in sperm production Abnormality in sperm production Abnormality in sperm function Abnormality in sperm function Obstruction in the ductal system Obstruction in the ductal system

34 Normal Sperm Morphology

35 Abnormal Morphology

36

37 Sperm How many are needed for fertilization? How many are needed for fertilization? Natural conception Natural conception 20,000,000 20,000,000 Intra-uterine insemination Intra-uterine insemination 1,000,000 1,000,000 In-vitro fertilization (IVF) In-vitro fertilization (IVF) 10,000 10,000 Intra-cytoplasmic sperm injection (ICSI) Intra-cytoplasmic sperm injection (ICSI) 1

38 Abnormalities of Sperm Production Genetic Genetic Y chromosome microdeletions Y chromosome microdeletions Damage to testes – anatomical Damage to testes – anatomical Cryptorchidism Cryptorchidism Varicocele Varicocele Infection Infection Mumps orchitis Mumps orchitis Gonadotoxins Gonadotoxins

39 Abnormalities of Sperm Function Antisperm antibodies Antisperm antibodies Genital tract inflammation Genital tract inflammation Prostatitis Prostatitis Varicocele Varicocele Failure of acrosome reaction Failure of acrosome reaction Problems with sperm binding/penetration Problems with sperm binding/penetration

40 Obstructions in Ductal System Vasectomy Vasectomy Congenital bilateral absence of the vas deferens Congenital bilateral absence of the vas deferens Epididymis/ejaculatory ducts Epididymis/ejaculatory ducts Congenital or acquired Congenital or acquired

41 Male Infertility - Lifestyle Tobacco Tobacco Marijuana Marijuana Alcohol Alcohol Cocaine Cocaine Steroids (can be permanent) Steroids (can be permanent) Heat Heat Exercise Exercise

42 Infertility: Initial Evaluation Eggs Eggs Ovulation (Progesterone) Ovulation (Progesterone) Egg quality (FSH, Estradiol) Egg quality (FSH, Estradiol) Sperm Sperm Presence Presence Quality Quality Gamete transport/Implantation Gamete transport/Implantation Hysterosalpingogram Hysterosalpingogram

43 Sperm: Semen Analysis Volume: > 2 mL Volume: > 2 mL Concentration: > 20,000,000 per mL Concentration: > 20,000,000 per mL Motility: > 50% Motility: > 50% Normal morphology: > 40% normal Normal morphology: > 40% normal Krueger strict criteria: > 14% normal Krueger strict criteria: > 14% normal Best predictor of fertilizing ability Best predictor of fertilizing ability

44 Infertility Treatments Improve Timing of Intercourse Improve Timing of Intercourse Intrauterine insemination (IUI) Intrauterine insemination (IUI) Clomiphene citrate (Clomid) + IUI Clomiphene citrate (Clomid) + IUI FSH + IUI FSH + IUI In Vitro Fertilization (IVF) In Vitro Fertilization (IVF) Standard IVF Standard IVF Egg donation + IVF Egg donation + IVF Egg Freezing + IVF Egg Freezing + IVF

45 Infertility Treatment Options IUI, FSH or FSH + IUI IUI, FSH or FSH + IUI Patients with unexplained infertility Patients with unexplained infertility Serhall et al, Fertil Steril 1988;49:602 TreatmentCyclesPregnancy Pregnancy per cycle IUI3012.7% FSH4936.1% FSH+IUI %

46 FSH (+) FSH=Follicle Stimulating Hormone How Does Clomid Work To Increase Egg Number? E2 (-) E2=Estradiol Developing follicle Clomid

47 FSH (+) FSH=Follicle Stimulating Hormone How Does Recombinant FSH Work To Increase Egg Number? E2 (-) E2=Estradiol Developing follicle

48 Intrauterine Insemination (IUI) Goal is to Maximize the Chance of Fertilization Increase Number of Eggs Position Sperm Closer to Eggs

49 In Vitro Fertilization

50 Historical Perspective 1978 Louise Joy Brown, first IVF baby 1978 Louise Joy Brown, first IVF baby 1981 Elizabeth Carr, first IVF baby in USA 1981 Elizabeth Carr, first IVF baby in USA 1983 First birth after egg donation 1983 First birth after egg donation 1985 First birth from cryopreserved embryo 1985 First birth from cryopreserved embryo 1985 Transvaginal ultrasound for follicle monitoring 1985 Transvaginal ultrasound for follicle monitoring 1990 First report of births after PGD 1990 First report of births after PGD 1990 First report of egg donation to older mothers 1990 First report of egg donation to older mothers 1992 First human birth after ICSI 1992 First human birth after ICSI

51 Who Needs IVF? Failed other treatments Failed other treatments Tubal damage Tubal damage Significant male factor Significant male factor Absent uterus Absent uterus Carriers of genetic diseases Carriers of genetic diseases Family Balancing Family Balancing Cancer patients Cancer patients Non-traditional Lifestyles Non-traditional Lifestyles

52 IVF Statistics U.S. programs offer IVF 422 U.S. programs offer IVF 134,260 cycles of ART treatment 134,260 cycles of ART treatment 9,649 donor oocyte cycles 9,649 donor oocyte cycles 38,910 deliveries (birth of 52,041 neonates) 38,910 deliveries (birth of 52,041 neonates) CDC 2005 National Report

53 In Vitro Fertilization (IVF)

54 Egg Retrieval

55

56 Fertilization

57 Fertilization 2 Pronuclei (2PN) 1 day after egg retrieval

58 Embryo Transfer

59

60 How Many Embryos are Transferred? Related to age and embryo quality Related to age and embryo quality <35 = 2 <35 = = = = = 3-4 >40 = up to 5 >40 = up to 5 For patients with 2 or more failed IVF cycles, or a poor prognosis, can add more based on clinical judgement For patients with 2 or more failed IVF cycles, or a poor prognosis, can add more based on clinical judgement

61 What Happens to the Other Embryos? Freeze Embryos Freeze Embryos Donate For Research/Stem Cells Donate For Research/Stem Cells Embryo Adoption Embryo Adoption Discard Discard

62 Special IVF Procedures Assisted hatching Assisted hatching Intracytoplasmic sperm injection (ICSI) Intracytoplasmic sperm injection (ICSI) Preimplantation genetic diagnosis (PGD) Preimplantation genetic diagnosis (PGD) Freezing Freezing Egg donation Egg donation Surrogacy Surrogacy

63 Assisted Hatching

64 Intracytoplasmic Sperm Injection (ICSI)

65 IVF Success Rates U.S. Fertility Centers (SART/CDC) U.S. Fertility Centers (SART/CDC) Female age Female age <35 – 37% (43%) <35 – 37% (43%) – 30% (36%) – 30% (36%) – 20% (27%) – 20% (27%) >40 – 11% (18%) >40 – 11% (18%)

66 IVF Statistics % singletons 65.1% singletons 32.9% twins 32.9% twins 4.4% triplets or more 4.4% triplets or more

67 Singleton Pregnancy

68 Twin Pregnancy

69 Triplet Pregnancy

70 Egg Donation

71 Egg donation IVF for two IVF for two Known/anonymous donor Known/anonymous donor <35 years old <35 years old Donor Donor Standard controlled ovarian hyperstimulation Standard controlled ovarian hyperstimulation Egg retrieval Egg retrieval Recipient Recipient Embryo transfer Embryo transfer

72 Who are candidates to be an egg donor ? years old (older if a friend or relative) years old (older if a friend or relative) FSH <10 FSH <10 Negative donor Negative donor Good health and genetic history Good health and genetic history Preferably prior egg donation experience Preferably prior egg donation experience How many eggs were produced? How many eggs were produced? Did pregnancy result? Did pregnancy result?

73 Who are candidates for egg donation ? Premature ovarian failure Premature ovarian failure Ovarian insufficiency (e.g. FSH>15 ) Ovarian insufficiency (e.g. FSH>15 ) Physiologic menopause Physiologic menopause Maternal age over 43 Maternal age over 43 History of poor egg/embryo quality or multiple IVF failures History of poor egg/embryo quality or multiple IVF failures

74 Egg Donation October 23, 1999 October 23, 1999 Selling Fashion Models' Eggs Online Raises Ethics Issues Selling Fashion Models' Eggs Online Raises Ethics Issues By CAREY GOLDBERG By CAREY GOLDBERG CAMBRIDGE, Mass. -- To the horror and disgust of mainstream infertility groups, a longtime fashion photographer has begun offering up models as egg donors to the highest bidders, auctioning their ova via the Internet to would-be parents willing to pay up to $150,000 in hopes of having a beautiful child. CAMBRIDGE, Mass. -- To the horror and disgust of mainstream infertility groups, a longtime fashion photographer has begun offering up models as egg donors to the highest bidders, auctioning their ova via the Internet to would-be parents willing to pay up to $150,000 in hopes of having a beautiful child.

75 Egg Donation Grade A: The Market for a Yale Womans Eggs When a Yale undergraduate explored becoming an egg donor for a wealthy couple willing to pay top dollar to the right candidate, she didn't realize how unsettling the process of candidacy would prove to be Grade A: The Market for a Yale Womans Eggs When a Yale undergraduate explored becoming an egg donor for a wealthy couple willing to pay top dollar to the right candidate, she didn't realize how unsettling the process of candidacy would prove to be by Jessica Cohen by Jessica Cohen

76

77 Gestational Surrogacy: Indications Absent uterus; congenital or iatrogenic Absent uterus; congenital or iatrogenic Abnormal uterus Abnormal uterus Medical contraindication to pregnancy Medical contraindication to pregnancy Recurrent pregnancy wastage Recurrent pregnancy wastage Repeated IVF failures with good embryos Repeated IVF failures with good embryos

78 Gestational Carriers Friends or relatives Friends or relatives Agencies Agencies Age less important Age less important Previous delivery and parenting Previous delivery and parenting Benign obstetrical history Benign obstetrical history Major psychological evaluation Major psychological evaluation Screening similar to recipients Screening similar to recipients

79 Initial screening-Egg and Sperm Donors (Known and Anonymous) Medical History (especially past history of donation in the case of egg donors so protocol and outcome can be reviewed) Medical History (especially past history of donation in the case of egg donors so protocol and outcome can be reviewed) Physical and Clinical Assessment Physical and Clinical Assessment Genetic Testing (as required based on Ethnic background and Family and Medical History) Genetic Testing (as required based on Ethnic background and Family and Medical History) Serologic (lab) Testing, STD tests, Drug Screening Serologic (lab) Testing, STD tests, Drug Screening Sexual partners of donors are screened for infectious diseases when donors are being evaluated for eligibility Sexual partners of donors are screened for infectious diseases when donors are being evaluated for eligibility Screening results for donors are good for 6 months only Screening results for donors are good for 6 months only

80 Anonymous Egg Donation Psychocologic Evaluation Personality Profile administered and evaluated by psychologist (PhD) or licensed social worker trained to work with donors with regards to donor's ability to "meet the demands of the egg donor role. Report sent to MD's office. Legal Contract Sent to MD's office stating that the Egg Donation Agreement has been "executed by all parties.

81 Known Egg/Sperm Donors Screenings set up through a specific agency Screenings set up through a specific agency Links known donors with psychologists and lawyers trained to perform above assessments and execute necessary legal contracts Links known donors with psychologists and lawyers trained to perform above assessments and execute necessary legal contracts Psych and legal assessment and clearance are especially important between known donors and recipients in which family relations or friendships may cloud the boundaries and guidelines necessary for a successful donor relationship and process Psych and legal assessment and clearance are especially important between known donors and recipients in which family relations or friendships may cloud the boundaries and guidelines necessary for a successful donor relationship and process

82 Danger to mother Danger to mother Decreased life expectancy of parents Decreased life expectancy of parents Quality of parenting Quality of parenting Is 55 a physiological limit? Is 55 a physiological limit? How old is too old?

83 Pregnancy in the Sixth Decade of Life USC experience: recipients of egg donation Mean age years Of the 77 women, 42 (54.5%) had live births Of the 77 women, 42 (54.5%) had live births 45 deliveries in 42 women 45 deliveries in 42 women Paulson, Tourgeman, Boostanfar et al, JAMA 2002:228;2320.

84 Pregnancy in the Sixth Decade of Life: Obstetric Complications Pre-eclampsia Pre-eclampsia 35% 35% Background Incidence 3-10% Background Incidence 3-10% Gestational Diabetes Gestational Diabetes 20% 20% Background Incidence 5% Background Incidence 5%

85 Pregnancy in the 6th decade of life: Conclusion There does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone There does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone

86 Genetic Testing Preconception Preimplantation Prenatal Postnatal

87 Preimplantation Genetic Diagnosis (PGD) Can test embryos for genetic abnormalities prior to implantation Can test embryos for genetic abnormalities prior to implantation Has been successfully used in diagnosing and preventing inherited genetic diseases like Cystic Fibrosis, Tay Sachs, Thalassemia, Sickle Cell Anemia and may be potentially used to screen for cancer mutations. Has been successfully used in diagnosing and preventing inherited genetic diseases like Cystic Fibrosis, Tay Sachs, Thalassemia, Sickle Cell Anemia and may be potentially used to screen for cancer mutations. Uses single cell (blastomere) at 8-cell stage Uses single cell (blastomere) at 8-cell stage

88 PGD First clinical application described by Handyside, Winston, and Hughes in 1990 By 2003, estimated >1000 PGD-defined live births (ESHRE Task Force, 2003)

89 Which Embryo is Disease-Free?

90 PGD – Clinical Indications Single gene defects Single gene defects Balanced translocations Balanced translocations Advanced maternal age (aneuploidy) Advanced maternal age (aneuploidy) Repetitive IVF failure Repetitive IVF failure Recurrent pregnancy loss Recurrent pregnancy loss Embryo selection Embryo selection

91 Achondroplasia ADPKD1 ADPKD2 Adrenoleukodystroph Age-related aneuploidies Alpha-thalassemia Alpha-1-antitrypsin Alport disease Amyloid precursor protein (APP) mutation ARPKD Becker muscular dystrophy Beta-thalassemia Charcot Marie Tooth disease Chromosomal translocations Congenital adrenal hyperplasia Cystic fibrosis Down syndrome Duchenne muscular dystophy Dystonia Epidermolysis bullosa Familial dysautonomia Fanconi anemia FAP Fragile X syndrome Gaucher disease Hemophilia A and B HLA genotyping HSNF5 mutation Huntington disease Hypophosphatasia Incontinentia pigmenti Kell disease Klinefelter syndrome LCHAD Lesch Nyhan syndrome Marfan syndrome Multiple epiphysial dysplasia Myotonic dystophy Myotubular myopathy NF1 and NF2 Norrie disease Osteogenesis imperfecta OTC deficiency P53 mutations PKU Retinitis pigmentosa SCA6 Sickle cell anemia Sonic hedgehog mutations Spinal muscular atrophy (SMA) Tay-Sachs disease Tuberous sclerosis Turner syndrome Von Hippel Lindau X-linked hydrocephaly X-linked hyper IgM syndrome

92 Day 3 Embryo Pre-Implantation Genetic Testing Stage

93 PGD – Timing of Biopsy Biopsy of a single cell can be performed from an 8-cell embryo after 3 days of culture in the laboratory

94 Fluorescence in situ hybridization (FISH) Fluorescence in situ hybridization (FISH) Aneuploidy/translocations and determining gender (5-10 chromosomes) Aneuploidy/translocations and determining gender (5-10 chromosomes) Polymerase chain reaction (PCR) Polymerase chain reaction (PCR) Specific single gene disorders Specific single gene disorders PGD

95 PGD The embryos would continue to grow for 2 more days in the laboratory, awaiting genetic analysis. The embryos would continue to grow for 2 more days in the laboratory, awaiting genetic analysis. The unaffected embryos are then transferred to the uterus at the blastocyst stage on day 5 of embryo culture and subsequently a child would be born unaffected from the screened genetic disease. The unaffected embryos are then transferred to the uterus at the blastocyst stage on day 5 of embryo culture and subsequently a child would be born unaffected from the screened genetic disease.

96 PGD Chromosome Panels Five Chromosome PGD 13, 18, 21, X, Y 13, 18, 21, X, Y Ten Chromosome PGD 8, 9, 13, 15, 16, 18, 21, 22, X, Y 8, 9, 13, 15, 16, 18, 21, 22, X, Y

97 Five Chromosome PGD

98

99 Ten Chromosome PGD 8 Red 9 Blue 15 Orange 16 Aqua 22 Green

100 Prenatal vs. Preimplantation Diagnosis PND PGD PND PGD Cells >100,000 1 Time 2 weeks6-10 hrs Accuracy 99% 99% Cost Covered ~$5,000

101 PGD Gender Selection: A Big Controversy!

102 Future considerations Oocyte cryopreservation Oocyte cryopreservation Pausing the biological clock Pausing the biological clock Cytoplasmic transfer Cytoplasmic transfer Donation of enucleated oocytes Donation of enucleated oocytes Reproduction without gametes Reproduction without gametes Use of nuclear material from somatic cells Use of nuclear material from somatic cells Donated or synthetic cytoplasm Donated or synthetic cytoplasm Reconstituted oocytes Reconstituted oocytes

103

104 Clinical Applications of Egg Freezing Oocyte cryopreservation could be a clinical tool for: Oocyte cryopreservation could be a clinical tool for: Women at risk of losing ovarian function Women at risk of losing ovarian function Women desiring fertility preservation (e.g. delayed maternity) Women desiring fertility preservation (e.g. delayed maternity) Eliminating ethical concerns of embryo cryopreservation Eliminating ethical concerns of embryo cryopreservation Solving the dilemma of abandoned frozen embryos in the IVF laboratory Solving the dilemma of abandoned frozen embryos in the IVF laboratory

105 Oocyte Cryopreservation Slow-freeze Technique Vitrification (Rapid Freeze) Technique

106 Oocyte Freezing: Where do we stand? First pregnancy after oocyte cryopreservation was reported by Chen in 1986 Less than 200 pregnancies have been achieved worldwide Less than 200 pregnancies have been achieved worldwide Survival rate of 80% and fertilization rates of 83%, however low pregnancy rates Although pregnancy rates might be improving, rates appear to be significantly less than those seen with standard IVF Although pregnancy rates might be improving, rates appear to be significantly less than those seen with standard IVF

107 Fertility Preservation Options Age Average Cost Time Requirement Success Rate Embryo Freezing After Puberty After Puberty $7,800; $350/year storage fees $7,800; $350/year storage fees 2-4 weeks 2-4 weeks ~40% per 3 embryos transferred under 35; lower in older women ~40% per 3 embryos transferred under 35; lower in older women Egg (Oocyte) Freezing After Puberty After Puberty $8,000; $350/year storage fees $8,000; $350/year storage fees 2-4 weeks 2-4 weeks Experimental; ~3% per egg frozen ~3% per egg frozen Ovarian Tissue Freezing Before and After Puberty Before and After Puberty $12,000; $350/year storage fees $12,000; $350/year storage fees Outpatient Surgical Procedure Outpatient Surgical Procedure Experimental; no live births to date no live births to date Ovarian Transposition Before or After Puberty Before or After Puberty Unknown Outpatient Surgical Procedure Outpatient Surgical Procedure ~50% for ovarian function, pregnancy rates unknown ~50% for ovarian function, pregnancy rates unknown GnRH Analog Treatment After Puberty After Puberty $500 per dose $500 per dose 1 dose per month in conjunction with chemotherapy 1 dose per month in conjunction with chemotherapy Experimental; study results vary: some show no benefit, others show success Experimental; study results vary: some show no benefit, others show success Donor Eggs Varies, usually Varies, usually $14,000-$20, weeks per cycle 2-4 weeks per cycle ART with Egg Donation, 40-50% Surrogacy Varies, usually Varies, usually $10,000 - $100,000 $10,000 - $100,000 Varies Similar to IVF, 20-30% Adoption Varies, usually Varies, usually $2,500 - $35,000 $2,500 - $35,000 Varies Greatly Varies Greatly Not Applicable Not Applicable

108 Thank you


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