Early detection of Cervical Cancer & Fertility Preservation

Early Detection of Cervical Cancer
& Fertility Preservation
DR GEETANJALI GARIEMA
M.B.B.S., M.S. (OBST. & GYNEC), F.MAS,
DRM (Dip. Reproductive Medicine, Germany),
Dip. Advanced Gynec Endoscopy (D.A.G.E.),D.MAS
Medical Director & Fertility Consultant – GlobalStar Fertility & Women Care Centre
https://globlstarivf.com

CERVICAL CANCER - INTRODUCTION
• Malignant tumour derived from the cells of “cervix uteri” which is
the lower part of the uterus
• begins with precancerous condition known as “DYSPLASIA”
• Easily detected in routine PAP Smear
• Completely Treatable
GlobalStar Fertility
https://Globalstarivf.com

INCIDENCE
• 2nd most common cancer in women worldwide
• Most Common women related cancer in India
• Occurs in 1 in 53 Indian women during their lifetime
• India accounts for 1/4th of Global Burden of cervical cancer

Normal Cervix Vs Cervical Cancer

Cervical Cancer & HPV
Human Papilloma Virus (HPV)
• The prevalence of HPV in cervical tumours is 99.7%
• High-risk HPV types include 16,18,31 and 41
• High risk HPV infection is necessary but insufficient for
cervical cancer

Human Papilloma Virus (HPV)
• Most common virus infecting the
reproductive tract.
• Cervical cancer is by far the most
common HPV- related disease.

Additional Risk Factors
• Early Onset of Sexual Activity
• Multiple sexual partners
• High-risk sexual partner
• History of sexually transmitted infection
• Use of oral contraceptives
• Immunosuppression
• Previous history of vulvar, vaginal or cervical squamous
dysplasia

Symptoms of Cervical Cancer
Early Stage Disease –
• Often no symptoms!
• Abnormal Vaginal discharge
• Abnormal bleeding
- Post-coital bleeding
- Abnormal menses
- Post-menopausal bleeding
Late Stage Disease –
• Pelvic or lower back pain
• Sciatica
• Weight loss
• Bowel or bladder fistula

Diagnosis of Cervical Cancer
• Cervical cytology (PAP Smear) – results may suggest
invasive cancer
• Abnormal cytology is an indication of colposcopic
evaluation & directed biopsy
• Diagnosis must be confirmed by biopsy

Screening Tests
Most common & effective screening for early diagnosis –
• PAP Test
- Conventional Slide Method
- Liquid Based Cytology (Thin Prep)
• HPV DNA Test

PAP Smear
When To Do –
• 3 years after the onset of sexual
intercourse
• No later than age 21
• Every 3 years until age 30
• After 30, repeat every 5 years
• Stop after age 65, if test is
negative in last 10 years
• Annual screening for women at high
risk
( As per American Cancer Society Guidelines)

HPV DNA TEST
• HPV DNA test also involves collecting cells from the cervix for lab
testing
• Sensitivity of Pap Test is 71%
• Sensitivity of HPV DNA test is 95%
• Collective sensitivity of Pap Test & HPV DNA test is 100%
• So between the age of 30 to 65, Cytology + HPV test is preferred

PREVENTION
This is one of the most preventable types of cancer
• Human Papilloma Virus (HPV) Vaccine – Bivalent (Cervarix) &
Quadrivalent (Gardasil)
• Safe sexual practice
• Routine Cervical Screening
• No smoking
• Healthy lifestyle & balanced diet to boost your immunity

FERTILITY PRESERVATION

Reasons for Increased Demand
In recent times –
• Increase incidence of cancer during the reproductive age
• Improved Survival & cure rates of cancer
• Increasing awareness & demand of fertility preservation interventions
• More women delaying motherhood to the age of 30s & 40s

Evaluation of Basic Factors
• Desire of patient to retain fertility potential
• Age, Obstetrical history, family history, history of infertility
• Extent of the patient’s cancer
ALWAYS REMEMBER –
Optimal cancer therapy should always supersede fertility preservation

Issues to be considered
• Overall prognosis of the patient
• The risk of sterility with the proposed treatment plan
• The potential risks of delaying chemotherapy
• The impact of future pregnancy upon the risk of tumour recurrence
• Impact of any hormonal manipulation on tumour itself
• The possibility of tumour contamination of the harvested tissues GlobalStar Fertility

The forgotten Female
• Only half of the oncologists discuss fertility preservation with patients
• ASRM offers guidelines for oncologists & fertility specialists
• Cancer specialist should inform patients about all the available options
• Refer them to fertility specialist

Effect of chemotherapy
In Females -
• Follicular destruction
• Ovarian fibrosis
• Premature ovarian failure
• Reduced E2 & P4 levels
In Males -
• Genetic & morphological damage of sperms

Chemotherapy Induced Gonadotoxicity
• Type, Duration & Dose
• Gonadotoxicity is almost irreversible
• Amenorrhea – ranges 0 - 100% , can be temporary or permanent
Younger age group – upto 71%
Older age group – upto 100%
• Risk of gonadal damage increases with age (less no of oocytes)

Radiotherapy Induced Gonadotoxicity
• Patient’s Age
• Dose of Radiation (Breaking point 300 cGy)
• Extent
• Type of Radiation (Abdominal, Pelvic external beam, Brachytherapy)

Dose of Radiation
• Breaking point is 300 cGy
• 11 – 13% had POF (premature ovarian failure) <300cGy
• 60 -63% had POF >300cGy
• >6Gy = Irreversible ovarian failure
• <2Gy = 50% of oocyte population is destroyed

Post Chemo/Radiotherapy Infertility Rate
In Females –
40 - 80% chance of loosing fertility during reproductive years
In Males –
30 -75% of male cancer patients become sterile after cancer treatment

Options for Preserving Fertility
In Females –
• Embryo Cryopreservation
• Oocyte Cryopreservation
• Ovarian tissue cryopreservation & Transplantation
• In vitro oocyte maturation
• Ovarian Transposition
• Pharmacological protection (GnRHa)
• Fertility – sparing surgical procedures
In Males –
• Sperm Cryopreservation – is the gold standard

Treatment options for Males
Post chemotherapy sperm sample holds high risk of genetic or
morphological sperm damage
• Sperm Cryopreservation is the only established & effective fertility
preservation method.
• Hormonal gonadal suppression is not recommended
• Gonadal shielding during radiation therapy
• Testicular tissue preservation and re-implantation is performed as
clinical trials

Treatment options for Females
• Embryo Cryopreservation
• Oocyte Cryopreservation
• Ovarian tissue cryopreservation &
Transplantation
• In vitro oocyte maturation
• Ovarian Transposition
• Pharmacological protection (GnRHa)
• Fertility – sparing surgical procedures

EMBRYO CRYOPRESERVATION
• Process of harvesting eggs, followed by In Vitro Fertilization of oocytes with
the sperms in lab & Freezing of all the resulting embryos for later
implantation.
• Requires 10-14 days of ovarian stimulation with gonadotropins from the
beginning of menstrual cycle.
• It is a short surgical procedure & requires partner sperms / donor sperm.
• Most established technique for fertility preservation in women

Success Rate in EMBRYO CRYOPRESERVATION
• Survival rate of thawed embryos = 35 - 90%
• Implantation Rate = 8 - 30%
• Cumulative Pregnancy Rate = 60%

OOCYTE CRYOPRESERVATION
• Process of harvesting & Freezing of unfertilized eggs/oocytes.
• Requires 10-14 days of ovarian stimulation from the beginning of menstrual
cycle.
• Advised for women who do not have a partner or do not wish to use donor
sperm
• Success rate is 3-4 times lower than standard IVF & embryo cryopreservation.

Success Rate of Oocyte Cryopreservation
Oocyte Vitrification –
• Survival Rate – 68%
• Fertilization – 48%
• Pregnancy Rate – 21%
Oocyte Freezing
• Pregnancy Rate – 2 to 11%
Oocyte Vitrification is preferred over freezing.

IN VITRO MATURATION ( IVM ) of Oocytes
• Freezing immature oocytes (primordial follicles)
• More oocytes become available for clinical treatment
• Gonadotropic hormones not required for stimulation
• Eliminates risk of ovarian stimulation

OVARIAN CRYOPRESERVATION & TRANSPLANTATION
• Freezing of ovarian tissue & reimplantation after cancer treatment.
• Ovarian stimulation not required.
• Does not require sexual maturity, so it is preferred in children.
• Not suitable when risk of ovarian involvement is high.

Ovarian Cortical Tissue Freezing
Slow-Freeze Protocol is more effective

Screening of ovarian tissue
• Best screening is under Light Microscopy
• Molecular markers can be used in rare cancers
• Test tissue before freezing & after thawing

Ovarian transplantation techniques
Orthotopic (Pelvic) Transplant
• Resumption of ovarian functions
• Spontaneous conception
• Sometimes require IVF
Heterotopic (subcutaneous)Transplant
• Requires IVF
• Embryo Transfer

OVARIAN SUPRESSION
• Done with GnRh analogues
• Insufficient evidence of effectiveness of GnRHa
• Offered in Ca Breast & Hodgkin’s lymphoma

OVARIAN TRANSPOSITION (OOPHOROPEXY)
• Ovaries are surgically moved away from radiation field & repositioned
• It minimises exposure & damage by radiation
• Technique not always successful due to many factors
• It prevents premature menopause & preserves fertility
• Pregnancy rates = 50 -75% spontaneously & 11% conception by IVF

CONCLUSION
• Assessment of risk of infertility in cancer patient
• Communication with patient
• Patient at risk of treatment induced infertility
• Patient interested in fertility preservation options
Refer to fertility specialist
Fertility preservation must be offered as early as possible after the
diagnosis of cancer & before starting any treatment

CONCLUSION
In Females –
• Embryo cryopreservation is most successful followed by oocyte
cryopreservation.
• Laparoscopic ovarian transposition is good option before pelvic
radiotherapy – technique not always successful due to many factors
• Ovarian suppression with GnRHa has insufficient evidence of effectiveness
• Ovarian tissue cryopreservation & transplantation – only method used in
children
In Males –
• Sperm Cryopreservation is the most effective method

Early detection of Cervical Cancer & Fertility Preservation

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