FERTILITY OPTIONS FOR EVERY PATIENT! · Fertility options for everyone! 5 2 IUI • Unexplained • Donor sperm • Mild male factor • Timing issues Donor sperm & eggs IVF • Male

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


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


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


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


Eggs


Regular menses


EGG GROWS PROGESTERONE

Case #1: Infertility workup - labs


Eggs


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


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


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


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?


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,



Eggs

Uterus & Tubes

(HSG, +/- U/S)

Sperm

(SA)


• 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


Case #1: Normal HSG



Eggs

Uterus & Tubes

(HSG, +/- U/S)

Sperm

(SA)


Case #1: Isolated teratozoospermia


Lifelabs

Case #1: Diagnosis = Unexplained


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

.


• 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.


• 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


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


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

23

PCRM laboratory

Slow sperm Fast sperm

Case #2: Single woman


24

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


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




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)


Case #2: Expectant management

NEJM (1982) 18:306(7), ACOG Committee Opinion 589 (2014)


Case #2: Expectant management < 5 years


12 month fertility rate

drops 10 – 15%





drops 10 – 15%





drops 10 – 15%

Embryo aneuploidy increases with age


Franasiak. et al. Fertil Steril (2013):101:656

30% aneuploid to 60% aneuploid = Double the aneuploidy in 5 years!

Case #2: Egg Freezing


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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..


2017 prediction model

Human Reproduction, Vol.32, No.4 pp. 853–859, 201736




37

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


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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



Donor Sperm


40

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


De Brucker M et al. Hum Reprod. 2009 Aug;24(8):1891-9

70% live birth rate in 6 cycles

http://www-ncbi-nlm-nih-gov.ezproxy.library.ubc.ca/pubmed/19369295



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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


43

42 yo woman &46 yo man “

“

Need donor eggs

• AMH low (3 pmol/L)• Tried IVF: got 2 eggs, no

normal fertilization

Donor Eggs


44

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


Case #4: Donor eggs

A single sperm is injected into a single mature egg


ICSI Intracytoplasmic Sperm Injection

Case #4: Age-related infertility


48

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)


49

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)


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




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Uterine factors

Same sex male couples, single males

Pregnancy risks


Fertility options for everyone!


52

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!

[email protected]

pacificfertility.ca


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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FERTILITY OPTIONS FOR EVERY PATIENT! · Fertility options for everyone! 5 2 IUI • Unexplained • Donor sperm • Mild male factor • Timing issues Donor sperm & eggs IVF • Male