Oncofertility:�Treatment Risks and Fertility Preservation Options for Patients

Rosemary O’Neil Semler, MA, RN, AOCNS

Perlmutter Cancer Center

NYU Langone Health

Treatment of cancer may affect fertility

Surgery

Resection of reproductive structures

Radiation

Fibrosis of reproductive structures �

Chemotherapy

Gonadal toxicity to oocytes/sperm

Fertility is important to cancer survivors

Many young cancer patients…

• Have not started or completed their families at the time of diagnosis
• Want to be parents after treatment
• Do not recall being told of risk of infertility or options for fertility preservation
• Are distressed or concerned about the possibility of infertility

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Bewtra, et al 2023; Himpe et al, 2023; Newton et al 2021; Benedict, 2016

Professional guidelines highlight the need for clinicians to address fertility

Division/Department

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Content Outline

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• Review the risks that treatment can pose to fertility for men and women

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• Describe fertility preservation options

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• Discuss collaboration of oncofertility nurses and genetic counsellors to provide care to our mutual patients

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Spermatogenesis and Ejaculation

Hwang, Ridgeway, & Lamb 2013; Schlegel 2007

Potential Effects of Treatment on Fertility

Impaired sperm production

Destruction of dividing spermatogonial stem cells and developing sperm

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Risk associated with:

• Chemotherapy

Alkylating agents, platinum analogues, anthracyclines

• Radiation therapy

Based on % testicular exposure & cumulative dose

Halpern et al 2020; Meistrich 2009

Potential Effects of Treatment on Fertility

Impaired sperm production

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Variation in extent of recovery

• Full recovery (normal sperm count)
• Oligospermia (low sperm count)
• Azoospermia (absence of sperm)

Variation in timing of recovery

• 1-5 years

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Howell & Shallet 2005; Kort et al 2014; Meistrich 2009

Potential Effects of Treatment on Fertility

Impaired sperm transport

Injury to pelvic ducts, blood vessels, nerves →

• Erectile Dysfunction
• Retrograde Ejaculation

Risk associated with:

• Pelvic surgery
• Pelvic radiation

Howell & Shallet 2005; Kort et al 2014; Meistrich 2009

Potential Effects of Treatment on Fertility

Pituitary gland dysfunction

Disruption hypothalamic-pituitary-testicular axis →

• Alterations in hormones needed to stimulate oocyte maturation

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Risk associated with:

• Cranial surgery
• Cranial radiation

Kort et al 2014; Levine et al 2012; Meirow et al 2010

Sperm Banking

• Performed at licensed sperm bank or andrology lab
• Semen collected by masturbation and analyzed
• Placed in vials, frozen and stored for future use

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3 collections

Abstain 2-5 days before each

$900-$1,200

McBride and Lipschultz, 2018; Nangia et al 2013; Trost & Brannigan 2012

Sperm Banking

Some patients may not be able to obtain a�specimen by masturbating

• Symptoms (pain, dyspnea)
• Medication side effects (opiates)
• Embarrassment
• Religious prohibitions

Electroejaculation�EEJ

Katz et al 2013; Moss et al 2016;Nangia et al 2013; Trost & Brannigan 2012

Sperm Banking

Some patients may not have any sperm found in their specimen

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>25% patients with testicular cancer, lymphoma, and leukemia have impaired spermatogenesis at diagnosis

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• Local effect of tumor in testes
• Systemic effects of disease
• Pre-existing defects in germ cells
• Endocrine alterations
• Immunologic disturbances

Testicular Sperm

Extraction TESE

Katz et al 2013; Moss et al 2016; Nangia et al 2013; Trost & Brannigan 2012

�Testicular Tissue Freezing

Investigational option for pre-pubertal boys

Testicular tissue biopsies

Future reimplantation

• Grafting tissue into testis
• Infusing a suspension of spermatogonial stem cells into testicular ducts

Newly diagnosed or recurrent tx

No live births to date

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Division/Department

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Picton, et al 2015; Fertility and Sterility, 2018

Female Reproductive Anatomy

Hoffman et al 2011; Oktem & Oktay 2008

# eggs=ovarian reserve

Effect of Age on Ovarian Reserve

10²

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Age (years)

Optimal

fertility

Declining

fertility

End of

fertility

# Follicles/

Eggs

Menopause

Adapted from Faddy et al 1992

Menses ≠ Fertility

Potential Effects of Treatment on Fertility

Depletion of ovarian follicle reserve

Premature ovarian failure: infertility & menopause at an early age

Jayasinghe et al 2018; Levine et al 2012; Meiro et al 2010

Gonadotoxic therapy

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60

Age (years)

# Follicles/

Eggs

Potential Effects of Treatment on Fertility

Chemotherapy

Impact based on drug, cumulative dose, and age

Biologics

Unknown evidence of risk

Radiation

Risk based on % ovary exposed and cumulative dose

Other factors

Age, obesity, family history, smoking, pre-treatment fertility

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It’s impossible to predict with certainty who will be affected!

Sellami et al, 2023; Roberts, et al 2015

Potential Effects of Treatment on Fertility

Uterine damage

Vascular changes, endometrial injury →

• Inability to support embryo implantation

Myometrial fibrosis → loss of elasticity →

• Inability to accommodate a growing fetus

Risk associated with:

• Pelvic radiation

Based on % uterine exposure and cumulative dose

Coubiere et al, 2023; Rosen et al, 2020

Potential Effects of Treatment on Fertility

Pituitary gland dysfunction

Disruption hypothalamic-pituitary-ovarian axis →

• Alterations in hormones needed to stimulate oocyte maturation

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Risk associated with:

• Cranial surgery
• Cranial radiation

Kort et al 2014; Levine et al 2012; Meirow et al 2010

Embryo and Oocyte Cryopreservation

ASRM 2013; Kort 2014; Rodriguez-Wallberg & Oktay 2015; Massarotti et all 2017

Under anesthesia

Ovarian�Stimulation

Egg Retrieval

IVF�In Vitro Fertilization

Daily hormone injections

~10 days

$7-12,000

No Fertilization

$8-14,000

Use of Frozen Embryos or Oocytes

Requires estrogen and progestin supplementation

• ~3 weeks before to prime the endometrial lining
• Continued through first trimester to support the pregnancy

Embryo Transfer

Recent legislation providing coverage

• In 2017, CT was the first state to pass legislation compelling insurers to provide coverage for fertility preservation for patients who are at risk of infertility from medical treatment.

• Since then, 18 additional states have passed similar legislation, including NY and NJ.

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• Not all patients have this coverage.

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Alliance for Fertility Preservation 2022

Embryo Cryopreservation Outcomes

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Patients Pursing IVF for Infertility

Live Birth Rate / Egg Retrieval Cycle

Preliminary National Summary Report 2022

www.sart.org

Probability of Live Birth 5 Years After Chemotherapy

Low Risk Chemotherapy (LRC)

High Risk Chemotherapy (HRC)

OC = Oocyte Cryopreservation

Lyttle Schumacher,B et al 2017

Ovarian Tissue Cryopreservation

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Khattak, et al 2022 ASRM 2014; Donnez & Dolmans 2017; Jensen et al 2017 ; Meirow et al 2016

• Option: prepubertal or can’t delay treatment and at high risk for POF
• First live birth reported in 2004
• ~200 live births w 28% success rate and 50% conceive naturally
• Unilateral laparoscopic oophorectomy
• 95% recover ovarian function
• Risk of re-introducing disease with some cancers

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Ovarian Suppression

GnRH agonists: leuprolide, goserelin, triptorelin

Mechanism of action is unclear

Suppression of FSH → ↓ follicle recruitment and maturation →protection from destruction

Administered as a monthly injection

Start 1-2 weeks before first chemotherapy

Will cause menopausal symptoms

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Lambertini et all, 2022; Lambertini et al, 2019

Ovarian Transposition

Prior to pelvic field radiation

• With IMRT to minimize ovarian dose
• Will not be able to conceive naturally
• Does not protect the uterus
• Also consider embryo/oocyte cryopreservation

Uterine Transposition

Prior to pelvic field radiation

• First reported in 2017
• Ovaries and uterus laparoscopically transpositioned to the upper abdominal wall and repositioned after treatment
• First NYU uterine transposition in 2024
• Several live births reported
• Egg freezing prior is recommended

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Christianson & Oktay 2019, Vieira et al 2021

Preimplantation Genetic Testing (PGT)

PGT-M: monogenic (single gene) disorders

• Tests for single gene disorders and hereditary cancer syndromes
• Allows for embryo selection

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PGT-A: aneuploidy (chromosomal abnormalities)

• Screen for whole chromosomal abnormalities
• Goal to increase live birth rates and decrease

early pregnancy loss

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Both involve biopsy of the trophectoderm of the

blastocyst

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ASRM 2018; Rosenwaks et al 2018; Munne et al 2019; ACOG 2020

Preimplantation Genetic Testing (PGT)

Many patient do not realize testing must be done on embryos.

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Patients who wish to do embryo selection should consider egg freezing at a younger age due to decrease in ovarian reserve that occurs with age.

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Philanthropic funding often does not include this group of patients.

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For patients with IVF coverage, about half have coverage for PGT-M testing.

Cost for PGT-A testing is ~ $300 per embryo.  Biopsy fee ranges $2000-$5000 per cycle.

Even if they have PGT-A/M coverage, many plans may not cover the biopsy fee. 

Q&A

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