Post on 06-Aug-2020
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FERTILITY OPTIONS FOR EVERY PATIENT!
DR. CAITLIN DUNNE
Clinical Assistant Professor, UBC
Co-Director, Pacific Centre for Reproductive Medicine
Objectives
Couples with unexplained infertility
Single women2
Same-sex couples3
Women with age-related infertility4
Surrogacy5
1
www.pacificfertility.ca2
Case #1: Unexplained infertility
www.pacificfertility.ca3
34 yo woman & 37 yo man “
“
Trying 18 months
• No reliable contraception for 4 years
• Feeling sad and frustrated
Definition
• Failure to conceive after 12 months of unprotected intercourse
• Affects 15% of couples
www.pacificfertility.ca4
Schorge JO, Schaffer JI, Halvorson LM, Hoffman BL, Bradshaw KD, Cunningham FG, Williams Gynecology, McGraw-Hill Inc. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med. 1995;333(23)
Infertility
Most conceive in 3 months
Case #1: Infertility workup
www.pacificfertility.ca5
Eggs
Uterus & Tubes
(HSG, U/S)
Sperm
(SA)
• History: Age, Ovulation• Labs: D3 FSH, AMH, AFC
Franasiak et al. Fertil Steril 2014; 101:656-63
Prevalence of aneuploidy
Case #1: Checking for ovulation
www.pacificfertility.ca7
Eggs
• History: Age, Ovulation• Labs: D3 FSH, AMH, AFC
Regular menses
www.pacificfertility.ca8
EGG GROWS PROGESTERONE
Case #1: Infertility workup - labs
www.pacificfertility.ca9
Eggs
• History: Age, Ovulation• Labs: D3 FSH, AMH, AFC
Fertility and Sterility. Elsevier; 2008 Apr;89(4):868–78
IVF live birth rates:
• Maximal when FSH < 7 IU/L• < 2% when FSH > 18 IU/L
Case #1: Day 3 FSH
Estradiol should be < 200pmol/L
Anti-Müllerian Hormone
Produced by pre-antral and antral follicles NOT by the dominant follicle
Constant throughout the cycle
www.pacificfertility.ca11
PLoS ONE. Public Library of Science; 2011;6(7):e22024. , Reprod Biomed Online. Elsevier; 2011 Aug;23(2):204–6.
Anti-Müllerian Hormone
AMH throughout the lifespan in women
Follicular gatekeeper
www.pacificfertility.ca12
PLoS ONE. Public Library of Science; 2011;6(7):e22024. , Reprod Biomed Online. Elsevier; 2011 Aug;23(2):204–6.
Should you order AMH?
AMH is most commonly useful for:IVF dosing Pre/Post ovarian surgery or chemotherapy
AMH is not a great predictor of fecundability
Any doctor can order AMH from LifeLabs70$No appointment
Valid any day of the cycleSlightly lower in OCP-users, pregnancy, post-partum, some ethnicitiesNot consistently influenced by smoking, vitamin D deficiency, physical exercise, alcohol use, age at menarche, socio-economic status
www.pacificfertility.ca13
Climacteric. 2015 Feb;18(1):47–52. ; Eur J Obstet Gynecol Reprod Biol. Elsevier; 2012 Aug;163(2):180–4; Human Reproduction. Oxford University Press; 2016 May;31(5):1034–45; Human Reproduction. Oxford University Press; 2017 Jan;32(1):208–14; Reprod Biomed Online. Elsevier; 2015 Oct;31(4):486–96.
AMH < 8pmol/L is low
High AMH ≠ PCOS
What is ‘normal’ ovarian reserve?
www.pacificfertility.ca14
Day 3 FSH Antral Follicle Count AMH
FSH < 7 – 10IU/L AFC > 7 AMH > 8pmol/L
* normals are highly age-dependent
Clinical Gynecological Endocrinology, Fritz&Speroff, 8th ed.,, Fertility and Sterility. Elsevier; 2008 Apr;89(4):868–78,
Case #1: Infertility workup
www.pacificfertility.ca15
Eggs
Uterus & Tubes
(HSG, +/- U/S)
Sperm
(SA)
• History: Age, Ovulation• Labs: D3 FSH, AMH, AFC
• Reminder about prophylaxis if patient has risk factors for post-procedure infection
• PID hx
• Hydrosalpinx
• Doxycycline 100mg PO BID for 3 – 5 days, begin day before the procedure
www.pacificfertility.ca16
Case #1: Normal HSG
Case #1: Infertility workup
www.pacificfertility.ca17
Eggs
Uterus & Tubes
(HSG, +/- U/S)
Sperm
(SA)
• History: Age, Ovulation• Labs: D3 FSH, AMH, AFC
Case #1: Isolated teratozoospermia
www.pacificfertility.ca18
Lifelabs
Case #1: Diagnosis = Unexplained
www.pacificfertility.ca19
30% of infertile couples
Their average monthly fecundity 1.8 – 3.8%
Tablets alone: ASRM (2013):Clomiphene + intercourse is no better than expectant managementPR with clomiphene 5.6% vs. 1.3 – 4.2% with expectant management
IUI alone: Cochrane Review (2016):IUI alone is no better than expectant management
Both together! Lancet (2018) RCT:Pregnancy rates 3x higher with three cycles of clomiphene or letrozole + IUI compared to expectant management
Practice Committee of the American Society for Reproductive Medicine Fertil Steril; 86, Suppl 4:S111-S114Cochrane Database Syst Rev 2016;2:Cd001838, Farquhar et al. Lancet 2018;391:441-50
.
Case #1: Diagnosis = Unexplained
• Standard basic treatment = tablets (e.g. clomiphene or letrozole) + intrauterine insemination
• AMIGOS Trial (2015) NEJM• 900 couples
• Gonadotropins vs. clomiphene vs. letrozole + IUI
• Letrozole PR was lower, but statistically non-inferior to clomiphene
www.pacificfertility.ca20Fertil Steril! 2013;100:341 , CPG: Use of CC in infertile women. ASRM.
Case #1: Diagnosis = Unexplained
• Standard basic treatment = tablets (e.g. clomiphene or letrozole) + intrauterine insemination
• JOGC (June 2019)• Meta-analysis showing letrozole and clomiphene are equally efficacious
for unexplained infertility
www.pacificfertility.ca21
Fertil Steril! 2013;100:341 , CPG: Use of CC in infertile women. ASRMJ Obstet Gynaecol Can 2019;41(6):832−834
Case #1: Unexplained infertility
www.pacificfertility.ca22
TREATMENT
• 3 cycles of letrozole2.5mg PO d3 – 7 (or 1-9) + IUI
• Expected pregnancy rate per cycle 8 – 12%
• Failing that, IVF
IUI
www.pacificfertility.ca
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PCRM laboratory
Slow sperm Fast sperm
Case #2: Single woman
www.pacificfertility.ca
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35 yo woman
I feel healthy, so I don’t have to worry about my eggs….right?
“
“
What are her options?
• The best predictor of egg quality is age
Women are having children later
www.pacificfertility.ca25
https://www2.gov.bc.ca/assets/gov/birth-adoption-death-marriage-and-divorce/statistics-reports/annual-reports/2015/pdf/annual-report-2015.pdf
CASE #2: Single woman
www.pacificfertility.ca26
Case #2: Single woman
www.pacificfertility.ca27
PREGNANT NOW!
DONOR SPERM
• IUI or IVF
PREGNANT LATER…
EGG FREEZING
EXPECTANT MANAGEMENT
IUI – Donor sperm in women with azoospermic husbands (NEJM)
Married fertility rates by 5-year age groups
(ACOG)
www.pacificfertility.ca28
Case #2: Expectant management
NEJM (1982) 18:306(7), ACOG Committee Opinion 589 (2014)
www.pacificfertility.ca29
Case #2: Expectant management < 5 years
NEJM (1982) 18:306(7), ACOG Committee Opinion 589 (2014)
12 month fertility rate
drops 10 – 15%
www.pacificfertility.ca30
Case #2: Expectant management < 5 years
NEJM (1982) 18:306(7), ACOG Committee Opinion 589 (2014)
12 month fertility rate
drops 10 – 15%
www.pacificfertility.ca31
Case #2: Expectant management < 5 years
NEJM (1982) 18:306(7), ACOG Committee Opinion 589 (2014)
12 month fertility rate
drops 10 – 15%
Embryo aneuploidy increases with age
www.pacificfertility.ca32
Franasiak. et al. Fertil Steril (2013):101:656
30% aneuploid to 60% aneuploid = Double the aneuploidy in 5 years!
Case #2: Egg Freezing
www.pacificfertility.ca
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Single women
Couples
Case #2: Egg freezing - how well does it work?
Doyle JO, Richter KS, Lim J, Stillman RJ, Graham JR, Tucker MJ. f cryopreserved oocytes and age at retrieval. Fertility
and Sterility. 2016;105(2):459–66.e2..
Case #2: Egg freezing - how well does it work?
2017 prediction model
Human Reproduction, Vol.32, No.4 pp. 853–859, 201736
Case #2: Egg freezing - how well does it work?
Case #2: Single woman
www.pacificfertility.ca
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What are her options?
• Waiting < 40 years old: • ~ 20 – 45% yearly fertility
rate• 60% embryo aneuploidy
• Egg freezing at age 35• 50 – 70% pregnancy rate
with 12-15 eggs• ~$7000 + medications
Case #3: Same sex female couple
www.pacificfertility.ca
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29 yo woman & 31 yo woman “
“
Need donor sperm
• Determine ovulation• HSG is reasonable
Basic ID, CMV screening
Counselor
Search for sperm donor online
Governed by Assisted Human Reproduction Act (AHRA), Food and Drugs Act
Anonymous, open/known, directed
www.pacificfertility.ca39
Case #3: Same sex female couple
Donor Sperm
www.pacificfertility.ca
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Single women
LGBTQ+
Infertile couples with male factor
Donor sperm: Cumulative live birth rate
6630 IUI cycles
1654 women
Average 14% delivery rate/cycle
87% 20-29
77% 30-34
www.pacificfertility.ca41
De Brucker M et al. Hum Reprod. 2009 Aug;24(8):1891-9
70% live birth rate in 6 cycles
Case #3: Same sex female couple
www.pacificfertility.ca
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Donor sperm
• Intrauterine insemination (IUI) for 3 – 6 cycles
• Keep costs in mind• $500 for IUI• $700 – $1000 per unit of
donor sperm
Case #4: Age-related infertility
www.pacificfertility.ca
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42 yo woman &46 yo man “
“
Need donor eggs
• AMH low (3 pmol/L)• Tried IVF: got 2 eggs, no
normal fertilization
Donor Eggs
www.pacificfertility.ca
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Infertile couples
LGBTQ+
Age
Costs vary but typically 11,000-16,500 USD for 6 frozen oocytes
Treatment costs in addition to cost of oocytesTotal $20 000 – $24 000 CAD
Oocyte donor selection, screening, information similar to donor sperm banks
Most are anonymous, some offer open identification
www.pacificfertility.ca45
Case #4: Donor eggs
A single sperm is injected into a single mature egg
www.pacificfertility.ca46
ICSI Intracytoplasmic Sperm Injection
Case #4: Age-related infertility
www.pacificfertility.ca
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Donor egg cycle• Endometrium is stimulated to
grow with oral estrace (2mg TID)
• Endometrium will respond even in menopause
• ‘Lining check’ ultrasound
• Vaginal progesterone (prometrium 200mg PV TID)
• Continue meds until 10 weeks (no endogenous hormone production)
www.pacificfertility.ca
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39 yo woman & 37 yo man “
“
3 prior surgeries
• 4 prior myomectomies• (hysteroscopic + open) Donor
egg embryos failed x 3
Case #5: Surrogacy (Gestational carrier)
Case #5: Surrogacy (Gestational carrier)
Assisted Human Reproduction Act (Federal law)
Illegal to pay, offer to pay or advertise to pay
Reimbursement for expenditures is allowed
Age ≥ 21 for surrogate motherHealthy
1 prior delivery
Age < 45
Physical and Psych screening normal
Legal, counselor requirements
www.pacificfertility.ca50
Case #5: Surrogacy (Gestational carrier)
www.pacificfertility.ca
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Uterine factors
Same sex male couples, single males
Pregnancy risks
Case #5: Surrogacy (Gestational carrier)
Fertility options for everyone!
www.pacificfertility.ca
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IUI• Unexplained• Donor sperm• Mild male factor• Timing issues
Donor sperm & eggs
IVF• Male factors• Tubal factors• Age• Unexplained
Egg freezing
• Elective fertility preservation
• Cancer• Surgery
• LGBTQ+• Age (eggs)• Male factor (sperm)
THANK YOU!
cdunne@pacificfertility.ca
pacificfertility.ca
www.pacificfertility.ca54
CC or IUI vs Expectant Management for UEI - RCT
Bhattacharya et al. BMJ 2008;337:1-8
580 women were randomised to:
• Expectant management (n=193)
• Clomiphene citrate (n=194)
• Unstimulated IUI (n=193)
Compared with expectant management, the OR for aLB was 0.79 (0.45 to 1.38) after CC and 1.46 (0.88 to 2.43) after unstimulated IUI
Letrozole
Most potent and highly selective non-steroidal third-generation inhibitor of final step in estrogen synthesis – aromatase
Suppresses >95% aromatase activity
Not FDA approved for fertility
2.5 mg x 5 days superior to CC for ovulation induction in PCO (28% vs 19% cumulative)1
2.5 mg x 9 days (extended protocol) may be superior to CC for unexplained (19% vs 11% clinical pregnancy rate)2
1. Legro et al. NEJM 2014 371(2): 119-292. Fouda et al. Reprd Biol Endo 2011;9(84)
Case #1: Regular menses = ovulation
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