Saturday, 15 November 2014

      DO NOT FORGET GONADAL FUNCTION...    

In patients with glomerular diseases, irreversible infertility may occur after treatment with alkylating agents, such as oral or intravenous cyclophosphamide and chlorambucil.


Here is a short summary of available recommendations for maintenance of fertility in patients needing alkylating drugs.  

Female sex
Serologic parameters of ovarian reserve include FSH, LH, and estradiol measured at the follicular phase on days 1–3 of the menstrual cycle, and progesterone measured at the luteal phase 7 days before the next menstruation to confirm ovulation.   

In the postpubertal female, options for gonad preservation include hormonal contraceptives, GRH agonists, and embryo and oocyte cryopreservation.  

Therapy with GRH agonists or analogs shows the most promising results for ovarian protection. The GRH agonists or analogs inhibit the pituitary–gonadal axis and subsequently, the complete ovarian suppression reduces the rate of oocyte maturation. Women develop amenorrhea at 3–8 weeks of treatment with GRH agonists or analogs, and menses generally return 6–10 weeks after withdrawal of GRH agonists or analogs.

Commercially available options include:

  - leuprolide 3.75 mg intramuscular every 4 weeks,
  - triptorelin 3.75 mg IM every 4 weeks, or
  - buserelin 200 mg 3 times a day intranasal

Ovarian protection with GRH agonists or analogs for 6 consecutive months during treatment with cytotoxic agents has been reported in patients with autoimmune diseases. The main adverse events associated with GRH agonist or analog therapy include injection site reactions (3–8%), hot flash, dry vagina, and irregular vaginal bleeding. Menopausal symptoms disappear generally 6–10 weeks after GRH agonist or analog withdrawal. The most serious side effect is loss of bone density. Concomitant calcium and vitamin D supplementation., bisphosphonate therapy, or transdermal estrogen supplementation are therefore necessary. Lupus flares may be induced by the increase of estrogen that is observed in the first two weeks of the start of GRH agonist or analog therapy. Anticoagulation in patients with SLE and/or the antiphospholipid syndrome for the first 3 weeks of GRH agonist or analog treatment seems prudent.

Male sex
Cryopreservation of spermatogonial stem cells for future autologous intratesticular transplantation is a preferable method for prepubertal boys, whereas sperm cryopreservation for future ARTs are options for postpubertal males. Importantly, regarding hormonal therapy for testicular preservation, several studies did not show a beneficial effect from hormonal treatment. 

Cryopreservation of semen and subsequent IVF is the only standard available option.

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