Bone Marrow Transplantation (2009) 00, 1–3& 2009 Macmillan Publishers Limited All rights reserved 0268-3369/09 $32.00 Paternity after directed collection of testicular sperm for in vitrofertilization after BMT for hematological malignancies Bone Marrow Transplantation (2009) 0, 000–000.
analyses with centrifuged pellet analysis, an elevated follicle-stimulating hormone (FSH) of 18.6 IU/l (normal2–8 IU/l), a LH of 6.9 IU/l (normal 2–12 IU/l and atestosterone of 641 ng/100 ml (normal 241–800 ng/100 ml).
Allogeneic and autologous BMT are routine treatments for To assess whether usable testicular sperm might be many men with advanced hematologic cancers. Although present to use with assisted reproduction, the patient associated with excellent survival rates, myeloablative conditioning regimens consisting of high-dose combination (FNA) ‘mapping’ with 15 cytologic specimens taken from alkylating agents and TBI in cases of allogenic transplants each testis.6 FNA mapping revealed three areas containing are generally thought to result in permanent infertility mature sperm (Figure 1a). The remaining 27 sites revealed in the vast majority of patients undergoing BMT.1 As a germ cell aplasia. Four months later, the patient underwent consequence, patients who survive and enter their repro- bilateral microdissection testicular sperm extraction that ductive years have limited opportunities for fatherhood if focused sperm retrieval on the earlier map locations.
they were not old enough to, or able to, bank sperm before Thirteen small biopsies were obtained that provided sufficient sperm for all oocytes during in vitro fertilization From our review of the English literature, there are eight reported cases of paternity after BM conditioning and sperm cryopreservation.7 At IVF, seven embryos were and BMT. Seven men established paternity after sponta- obtained after fertilization and four were implanted. The neous recovery of natural fertility2–4 and one achieved couple delivered healthy twins, one male and one female.
paternity with the use of assisted reproduction (ART).5 We Case 2 is a 33-year-old patient who had a history of present two novel cases of biological paternity using testis childhood Hodgkin’s disease and was referred for evalua- sperm and assisted reproduction in men without sperm tion of infertility and azoospermia. He was diagnosed in the ejaculate (azoospermia) after BMT for hematologic with Hodgkin’s disease (Stage IIB) at age 12. He was treated with chemotherapy (MOPP, ABVD) and radio- Case 1 is a 38-year-old patient who presented for therapy with consequent disease remission. At age 17, he fertility care with persistent azoospermia after aggressive relapsed and underwent a CBV conditioning regimen chronic myelogenous leukemia (CML) treatment. He was followed by reinduction with two cycles of MOPP/AV diagnosed with CML 7 years prior to presentation and hybrid chemotherapy and autologous BMT. Upon pre- initially treated with hydroxyurea and a-IFN. The addition sentation for fertility care, the patient was in CR with of low-dose cytarabine subsequently induced disease residual acid reflux under good control. A physical exami- remission. The patient experienced a blast crisis 2 years nation revealed a healthy, well developed male with small later that was treated with plicamycin, high-dose cytar- testes (12 ml right; 12 ml left) of normal consistency. A left abine, etoposide and hydroxyurea. The patient attempted grade II varicocele was observed. A routine semen analysis to bank sperm before this treatment, but a semen analysis was significant for normal volume azoospermia. No sperm showed azoospermia. This blast crisis did not resolve and were found on centrifuged pellet analysis. Endocrine the patient then received decitabine and daunorubicin parameters revealed an FSH of 25.0 IU/l, LH of 6.6 IU/l followed by total-body irradiation and allogeneic BMT and a testosterone of 566 ng/100 ml.
(HLA-B mismatch, unrelated donor). Six months post- Again, to determine the patient’s candidacy for assisted transplant the patient developed steroid responsive GVHD.
reproduction testicular FNA ‘mapping’ was performed He was subsequently medically managed and presented for under local anesthesia in the office. The diagnostic FNA fertility care 4.5 years after the transplantation, on procedure revealed mature spermatozoa in 3 of 30 sites carvedilol and verapamil for chemotherapy-induced cardi- sampled (Figure 1b). Nine months later the patient UNCORRECTED PROOF
omyopathy, trimethoprim/sulfamethoxazole and topical 5- underwent microdissection testicular sperm extraction fluorouracil for disseminated actinic superficial poroker- under local anesthesia and i.v. sedation that focused on sperm retrieval to FNA map locations showing sperm.
On physical examination he appeared healthy. Scrotal Sufficient motile sperm were isolated to cover all eggs at examination revealed a normal phallus and small, soft IVF, and extra sperm were cryopreserved. At IVF, six testicles (10 ml right; 12 ml left). The vasa deferentia and mature eggs were harvested from the patient’s 33-year-old epididymides were palpably normal. No clinical varicocele partner. ICSI resulted in two fertilized eggs that were or adenopathy was apparent. Laboratory examination was implanted and an ongoing clinical singleton pregnancy was significant for azoospermia on two consecutive semen


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Pharmaceutical Law & Industry Report® Reproduced with permission from Pharmaceutical Law & Industry Report, 11 PLIR , 9/20/13. Copyright ஽ 2013 byThe Bureau of National Affairs, Inc. (800-372-1033) http://www.bna.comInterpreting Actavis , Young said that even though thegeneric defendants in the Nexium case did not receivePlaintiffs’ Antitrust Claims May Proceedany kind of dir

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