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Induction of Ovulation For Cancer patientHesham Al-Inany, M.D, PhD (Amsterdam)

Outline of this talk

• Introduction

• practical protocol

Why this talk?

• the survival rates for women with cancers have increased significantly during the past decades (Jemal et al., 2004) due to improved diagnosis and treatment

For example: Cancer Breast

•Survival rates for breast cancer have risen in recent years, reaching 81–87%. (Martos et al., 2009)

Another factor: Changing trend

•Being a hormonal dependent tumor, it has been generally assumed that subsequent pregnancies are detrimental because of the high levels of circulating estrogens.

•However, a recent meta-analysis has shown that pregnancy after breast cancer paradoxically improves survival (Azim et al., 2011).

Not all cancers and their treatments may affect fertility at all, the effect may be temporary

or permanent, immediate or occur later with the woman’s

fertility potential shortened by a premature menopause.

Commonest Types of cancer in females in reproductive years.

• Lymphomas.

• Leukaemias. [including pre-bone marrow transplantation radiation TBR.]

•Breast Cancer.

•Endometrial/Cervical cancer[Sonmezer and Oktay 2004]

Factors to consider Include:-

• Type and extent of the disease.• Age, and any previous fertility.• Use of surgical removal/ablation of a vital

reproductive organ or one playing a role in reproduction in treatment.

So ??

• Inducing ovulation in patients with cancer should be considered cautiously and approached differently compared to that in women without cancer.

Outline of this talk

• Introduction

• practical protocol

How?

•Repeated cycles of ovulation induction should be avoided

•Scope of IVF should be widened

If IVF is refused?!!

• Limit ovarian damage

•Rational:- Stop ovarian function as dividing cells maybe more sensitive to cytotoxic effects but under10% growing at a time.

•GnRHa depot (Lupron or others)

Vitrification

• Is an alternative option

Single IVF cycle

• it is crucial that as many cryopreserved embryos or oocytes as possible be obtained in this cycle for future use.

Challenges

• should be initiated before chemotherapy or radiation therapy since both therapies have deleterious effects on the ovarian reserve ending up with premature ovarian failure and subsequent infertility (Lee, 2006).

Which protocol?

• In the same time , not to delay starting chemotherapy or radiotherapy

• This can be ideally fulfilled with the use of GnRH antagonist protocol (Friedler et al., 2012).

Which day?

• Ideally day2,3,4 of cycle

• If luteal phase, recent evidence supports starting with antagonist for few days then O.I after E2 assay

Expected duration?

• Two weeks maximum

• Then OPU

•Rest 2-5 days before starting chemotherapy

Dose of Gn?

•Aggressive stimulation is needed

• Target to get 15-20 follicles

•Chance of OHSS is very low as no ET will be done

Challenge II

• The reproductive capacity of patients with cancers seems to be diminished

• subjects with cancers are more likely to be poor responders (Quintero et al., 2010).

Why?

• cancer is associated with an increased catabolic state which may affect the hypothalamic pituitary axis resulting in hypothalamic dysfunction and a decrease in gonadotropin levels, thereby impairing the reproductive capacity (Agarwal and Said. 2004).

• a possible role of BRCA1 as an important factor responsible for the impairment in double strand DNA break repair and women’s infertility (Oktay et al., 2010).

Challenge III

• Induction of ovulation is typically associated with increased levels of estradiol.

• This can be detrimental in women with estrogen sensitive cancers as breast cancers and endometrial cancer

How to solve ?

•Aromatase Inhibitors

• peak estradiol level is lower in protocols that use aromatase inhibitors for ovarian stimulation (Oktay et al., 2005; Verpoest et al., 2006).

Best regimen

• high doses of gonadotropins (FSH 375 U/day) in a GnRH antagonist protocol in combination with letrozole (Ben-Haroush et al. 2011)

triggering

• triggering with GnRH agonists improved the safety of the protocol without any cases of severe ovarian hyperstimulation (Bodri et al., 2010).

Few days later

•You may start radiotherapy or chemotherapy course

Long term safety?

• induction of ovulation doesn’t seem to increase risk of recurrence compared to controls, however, still more studies and longer follow up are needed. (Azim et al, 2009)

Newborn Safety ?

• Till now, no evidence of any teratogenic effect of ovlulation induction in cancer patient

Challenge IV

•How to convince oncologist?

• It needs a multidisciplinary approach

•Authorised bodies can only push this forward

Approach

•We can minimize the devastating sequelae of cancer

Conclusion

•Very infrequent challenge but serious one

•weigh benefits and risks

•Needs team work

Thank youDr. Hesham Al-Inany MD, PhD

e-mail : kaainih@yahoo.com