does testicular sperm improve icsi outcome in patients with necrozoospermia?

1
DOES TESTICULAR SPERM IMPROVE ICSI OUTCOME IN PATIENTS WITH NECROZOOSPERMIA? Luciano Negri, Renzo Benaglia, Antonella Smeraldi, Francesca Menduni, Paolo E. Levi Setti Department of Gynecology, Operative Unit of Gynecology and Reproductive Medicine. IRCCS, Istituto Clinico Humanitas. Rozzano-Italy Introduction: Necrozoospermia affects 0.2% to 0.4% of men undergoing infertility work-up and relates to a large variety of etiologies. Intra- cytoplasmic sperm injection (ICSI) has proven to be a very successful treatment, even in the most severe forms of male infertility. Nevertheless, necrozoospermia has been associated with ICSI failure (Sherins et al., 1995; Tournaye et al., 1996; Poe-Zeigler et al., 1997; Stalf et al., 2005) and injection of testicular spermatozoa (ICSI-TESE) has been suggested to treat this form of male infertility. Material and Methods: ICSI outcomes in 279 couples submitted to 635 oocyte retrievals have been retrospectively analyzed. All male partners suffered from asthenozoospermia with necrozoospermia (sperm viability ranging from 2% to 40%). Five-hundred and fty cycles with ejaculated fresh sperm (459 with fresh oocytes, 91 with thawed oocytes) were matched with 196 cycles using cryopreserved testicular sperm (176 with fresh oocytes, 20 with thawed oocytes). Fifty-seven couples performed both ICSI and ICSI-TESE. Results: Female age at oocyte retrieval (range 25-46.2 y.) was 35.9 3.7 in ICSI group vs. 36.1 3.6 in ICSI-TESE group (n.s.). There was no difference was observed between the two groups in basal FSH (7.6 2.9 vs. 7.4 2.2 mU/ml) nor in the number of oocytes retrieved (9.7 5.3 vs.10.2 5.5), injected (4.3 2.9 vs. 4.3 2.5), fertilized (2.7 2,1 vs. 2.5 1.8), embryos transferred (2.2 0.8 vs. 2.1 0.8) and embryo frozen (206 vs. 49). Fourty-ve (8.1%) fertilization failures occurred in the ICSI group vs. 12 (6.1%) in the ICSI-TESE group (n.s.). Five-hundred and fty embryo-transfers (976 fresh embryos, 154 thawed oocytes, 105 thawed embryos) in the ICSI group and 198 in the ICSI-TESE group (349 fresh embryos, 46 thawed oocytes, 30 thawed embryos) were carried out, leading to 116 (21.1%) and 68 (34.6%) clinical pregnancies per cycle with oocyte retrieval (p¼0.0002). The implantation rate was 12.1% in the ICSI group vs 20.7% in the ICSI-TESE group (p<0.0001). Eighty-six women in the ICSI group had a live-birth delivery vs. 48 in the ICSI- TESE group (delivery rate / oocyte retrieval 15.6% vs. 24.5%; p¼0.007). Conclusions: A high rate of non-viable spermatozoa in the semen suggests a profound deterioration of sperm cell functions and our data highlight the risk of reduced ICSI successes in necrozoospermic patients. The use of testicular sperm in these patients, although cryopreserved, provides a signicantly higher success rate. Although to be conrmed in a rando- mised trial this result is new and relevant data in patient counselling. doi:10.1016/j.placenta.2011.07.018 EVALUATION AND MANAGEMENT OF RECURRENT PREGNANCY LOSS Marianna Pina Rambaldi a , Federico Mecacci a , Michael J. Paidas b a Azienda Ospedaliera Universitaria Careggi, Dipartimento Assistenziale Integrato Materno Infantile, Firenze, Italia; b Yale Women and Children's Center for Blood Disorders, Yale University School of Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, New Haven, Connecticut The overall risk of miscarriage is approximately 15% in an unselected population and in women after a rst abortion, but rises to 17-31% after two consecutive losses and to 25-46% after 3 or more. Aneuploidy is the most common cause of embryonic loss before 10 weeks of gestation. Genetic evaluation of products of conception is recommended after each abortion and abnormal results can be detected in 50-70% of cases [1]. The parental karyotype is abnormal in 2-4% of all couples with recurrent pregnancy loss (RPL) and frequencies up to 10% are found when other common causes are rst excluded [2, 3]. Folate deciency has been associated with aneuploidy and supplementation is recommended in all patients with RPL [4]. Thyroid dysfunction has been implicated in pregnancy loss and therefore must be diagnosed and treated. While luteal phase deciency has been associated with RPL, clinical trials have provided mixed results regarding efcacy of treatment with progesterone supplementation in women with unex- plained RPL [3]. Polycystic ovarian syndrome is frequently associated with RPL (36-56%) but treating these patients with metformin is of unclear benet [5-7]. Antiphospholipid syndrome has been diagnosed in 15-40% of women with RPL and screening is recommended [8]. Meta-analyses suggest that these patients could benet from a combination treatment of heparin and low dose aspirin [9, 10]. Factor V Leiden deciency is associated with a small increased risk of fetal loss, but other common mutations such as MTHFR and prothrombin gene mutation G20210A are not [11, 12]. Widespread screening for inherited thrombophilia appears to have limited value. After evaluation, RPL remains unexplained in approximately one half of couples. Following previous contrasting results, recent randomized trials demonstrate that treatment with low molecular weight heparin and/or aspirin do not improve pregnancy outcome in women with unexplained RPL [13, 14]. More intensive investigation of genetic etiologies of fetal loss is likely to reduce the proportion of unexplained recurrent fetal loss [15]. References [1] Hogge WA, et al. The clinical use of karyotyping spontaneous abortions. Am J Obstet Gynecol 2003;189(2):397400. discussion 400-2. [2] Carp H, et al. Parental karyotype and subsequent live births in recurrent miscarriage. Fertil Steril 2004;81(5):1296301. [3] ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24, February 2001. (Replaces Technical Bulletin Number 212, September 1995). American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet, 2002; 78(2): p. 17990. [4] George L, et al. Plasma folate levels and risk of spontaneous abortion. JAMA 2002;288(15):186773. [5] Thatcher SS, Jackson EM. Pregnancy outcome in infertile patients with poly- cystic ovary syndrome who were treated with metformin. Fertil Steril 2006; 85(4):10029. [6] Jakubowicz DJ, et al. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87(2):5249. [7] Legro RS, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007;356(6):55166. [8] Laurino MY, et al. Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J Genet Couns 2005;14(3):16581. [9] Ziakas PD, Pavlou M, Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta- analysis. Obstet Gynecol 2010;115(6):125662. [10] Mak A, et al. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford) 2010;49(2):2818. [11] Lissalde-Lavigne G, et al. Factor V Leiden and prothrombin G20210A poly- morphisms as risk factors for miscarriage during a rst intended pregnancy: the matched case-control NOHA rststudy. J Thromb Haemost 2005;3(10): 217884. [12] Roque H, et al. Maternal thrombophilias are not associated with early preg- nancy loss. Thromb Haemost 2004;91(2):2905. [13] Kaandorp SP, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med 2010;362(17):158696. [14] Clark P, et al. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in womenwith recurrent miscarriage. Blood 2010;115(21):41627. [15] Reddy U. Stillbirth Collaborative Research Network: genetic changes identied in stillbirths using molecular cytogenetic technology. Am J Obstet Gynecol 2011;204. p. s2. doi:10.1016/j.placenta.2011.07.019 THE CONCOMITANT PRESENCE OF DEEP INFILTRATING ENDOMETRIOSIS WORSENS THE ENDOMETRIOMA-RELATED NEGATIVE IMPACT ON OVARIAN RESERVE AND THE NUMBER OF RETRIEVED OOCYTES Ottolina Jessica, Papaleo Enrico, Viganò Paola, Brigante Claudio, Marsiglio Elena, De Michele Francesca, Candiani Massimo Centro Scienze Natalità, Obstetrics and Gynecology Unit, San Raffaele Scientic Institute, Milan, Italy Introduction: Endometriosis-associated infertility is known to result in reduced ovarian response, fewer oocytes being available for fertilization Abstracts / Placenta 32 (2011) S276S282 S278

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Abstracts / Placenta 32 (2011) S276–S282S278

DOES TESTICULAR SPERM IMPROVE ICSI OUTCOME IN PATIENTS WITHNECROZOOSPERMIA?

Luciano Negri, Renzo Benaglia, Antonella Smeraldi, FrancescaMenduni, Paolo E. Levi SettiDepartment of Gynecology, Operative Unit of Gynecology andReproductive Medicine. IRCCS, Istituto Clinico Humanitas. Rozzano-Italy

Introduction: Necrozoospermia affects 0.2% to 0.4% of men undergoinginfertility work-up and relates to a large variety of etiologies. Intra-cytoplasmic sperm injection (ICSI) has proven to be a very successfultreatment, even in the most severe forms of male infertility. Nevertheless,necrozoospermia has been associated with ICSI failure (Sherins et al., 1995;Tournaye et al., 1996; Poe-Zeigler et al., 1997; Stalf et al., 2005) andinjection of testicular spermatozoa (ICSI-TESE) has been suggested to treatthis form of male infertility.

Material and Methods: ICSI outcomes in 279 couples submitted to 635oocyte retrievals have been retrospectively analyzed. All male partnerssuffered from asthenozoospermia with necrozoospermia (sperm viabilityranging from 2% to 40%). Five-hundred and fifty cycles with ejaculated freshsperm (459 with fresh oocytes, 91 with thawed oocytes) were matched with196 cycles using cryopreserved testicular sperm (176 with fresh oocytes, 20with thawedoocytes). Fifty-seven couples performedboth ICSI and ICSI-TESE.Results: Female age at oocyte retrieval (range 25-46.2 y.) was 35.9 � 3.7 inICSI group vs. 36.1�3.6 in ICSI-TESE group (n.s.). Therewasnodifferencewasobserved between the two groups inbasal FSH (7.6� 2.9 vs. 7.4� 2.2mU/ml)nor in the number of oocytes retrieved (9.7� 5.3 vs.10.2� 5.5), injected (4.3� 2.9 vs. 4.3� 2.5), fertilized (2.7�2,1 vs. 2.5�1.8), embryos transferred (2.2� 0.8 vs. 2.1 � 0.8) and embryo frozen (206 vs. 49). Fourty-five (8.1%)fertilization failures occurred in the ICSI group vs. 12 (6.1%) in the ICSI-TESEgroup (n.s.). Five-hundred and fifty embryo-transfers (976 fresh embryos,154 thawed oocytes, 105 thawed embryos) in the ICSI group and 198 in theICSI-TESE group (349 fresh embryos, 46 thawed oocytes, 30 thawedembryos) were carried out, leading to 116 (21.1%) and 68 (34.6%) clinicalpregnancies per cycle with oocyte retrieval (p¼0.0002). The implantationrate was 12.1% in the ICSI group vs 20.7% in the ICSI-TESE group (p<0.0001).Eighty-sixwomen in the ICSI grouphad a live-birthdelivery vs. 48 in the ICSI-TESE group (delivery rate / oocyte retrieval 15.6% vs. 24.5%; p¼0.007).Conclusions: A high rate of non-viable spermatozoa in the semen suggestsa profound deterioration of sperm cell functions and our data highlight therisk of reduced ICSI successes in necrozoospermic patients. The use oftesticular sperm in these patients, although cryopreserved, providesa significantly higher success rate. Although to be confirmed in a rando-mised trial this result is new and relevant data in patient counselling.

doi:10.1016/j.placenta.2011.07.018

EVALUATION AND MANAGEMENT OF RECURRENT PREGNANCY LOSS

Marianna Pina Rambaldi a, Federico Mecacci a, Michael J. Paidas b

a Azienda Ospedaliera Universitaria Careggi, Dipartimento AssistenzialeIntegrato Materno Infantile, Firenze, Italia; b Yale Women and Children'sCenter for Blood Disorders, Yale University School of Medicine,Department of Obstetrics, Gynecology and Reproductive Sciences, NewHaven, Connecticut

The overall risk of miscarriage is approximately 15% in an unselectedpopulation and inwomen after a first abortion, but rises to 17-31% after twoconsecutive losses and to 25-46% after 3 or more. Aneuploidy is the mostcommon cause of embryonic loss before 10 weeks of gestation. Geneticevaluation of products of conception is recommended after each abortionand abnormal results can be detected in 50-70% of cases [1]. The parentalkaryotype is abnormal in 2-4% of all couples with recurrent pregnancy loss(RPL) and frequencies up to 10% are found when other common causes arefirst excluded [2, 3]. Folate deficiency has been associated with aneuploidyand supplementation is recommended in all patients with RPL [4]. Thyroiddysfunction has been implicated in pregnancy loss and therefore must bediagnosed and treated. While luteal phase deficiency has been associated

with RPL, clinical trials have provided mixed results regarding efficacy oftreatment with progesterone supplementation in women with unex-plained RPL [3]. Polycystic ovarian syndrome is frequently associated withRPL (36-56%) but treating these patients with metformin is of unclearbenefit [5-7]. Antiphospholipid syndrome has been diagnosed in 15-40% ofwomen with RPL and screening is recommended [8]. Meta-analysessuggest that these patients could benefit from a combination treatment ofheparin and lowdose aspirin [9,10]. Factor V Leiden deficiency is associatedwith a small increased risk of fetal loss, but other common mutations suchas MTHFR and prothrombin gene mutation G20210A are not [11, 12].Widespread screening for inherited thrombophilia appears to have limitedvalue. After evaluation, RPL remains unexplained in approximately one halfof couples. Following previous contrasting results, recent randomized trialsdemonstrate that treatment with low molecular weight heparin and/oraspirin do not improve pregnancy outcome in women with unexplainedRPL [13,14].More intensive investigation of genetic etiologies of fetal loss islikely to reduce the proportion of unexplained recurrent fetal loss [15].

References

[1] Hogge WA, et al. The clinical use of karyotyping spontaneous abortions. Am JObstet Gynecol 2003;189(2):397–400. discussion 400-2.

[2] Carp H, et al. Parental karyotype and subsequent live births in recurrentmiscarriage. Fertil Steril 2004;81(5):1296–301.

[3] ACOG practice bulletin. Management of recurrent pregnancy loss. Number 24,February 2001. (Replaces Technical Bulletin Number 212, September 1995).American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet,2002; 78(2): p. 179–90.

[4] George L, et al. Plasma folate levels and risk of spontaneous abortion. JAMA2002;288(15):1867–73.

[5] Thatcher SS, Jackson EM. Pregnancy outcome in infertile patients with poly-cystic ovary syndrome who were treated with metformin. Fertil Steril 2006;85(4):1002–9.

[6] Jakubowicz DJ, et al. Effects of metformin on early pregnancy loss in thepolycystic ovary syndrome. J Clin Endocrinol Metab 2002;87(2):524–9.

[7] Legro RS, et al. Clomiphene, metformin, or both for infertility in the polycysticovary syndrome. N Engl J Med 2007;356(6):551–66.

[8] Laurino MY, et al. Genetic evaluation and counseling of couples with recurrentmiscarriage: recommendations of the National Society of Genetic Counselors. JGenet Couns 2005;14(3):165–81.

[9] Ziakas PD, Pavlou M, Voulgarelis M. Heparin treatment in antiphospholipidsyndrome with recurrent pregnancy loss: a systematic review and meta-analysis. Obstet Gynecol 2010;115(6):1256–62.

[10] Mak A, et al. Combination of heparin and aspirin is superior to aspirin alone inenhancing live births in patients with recurrent pregnancy loss and positiveanti-phospholipid antibodies: a meta-analysis of randomized controlled trialsand meta-regression. Rheumatology (Oxford) 2010;49(2):281–8.

[11] Lissalde-Lavigne G, et al. Factor V Leiden and prothrombin G20210A poly-morphisms as risk factors for miscarriage during a first intended pregnancy:the matched case-control ‘NOHA first’ study. J Thromb Haemost 2005;3(10):2178–84.

[12] Roque H, et al. Maternal thrombophilias are not associated with early preg-nancy loss. Thromb Haemost 2004;91(2):290–5.

[13] Kaandorp SP, et al. Aspirin plus heparin or aspirin alone in women withrecurrent miscarriage. N Engl J Med 2010;362(17):1586–96.

[14] Clark P, et al. SPIN (Scottish Pregnancy Intervention) study: a multicenter,randomized controlled trial of low-molecular-weight heparin and low-doseaspirin in women with recurrent miscarriage. Blood 2010;115(21):4162–7.

[15] Reddy U. Stillbirth Collaborative Research Network: genetic changes identifiedin stillbirths using molecular cytogenetic technology. Am J Obstet Gynecol2011;204. p. s2.

doi:10.1016/j.placenta.2011.07.019

THE CONCOMITANT PRESENCE OF DEEP INFILTRATING ENDOMETRIOSISWORSENS THE ENDOMETRIOMA-RELATED NEGATIVE IMPACT ONOVARIAN RESERVE AND THE NUMBER OF RETRIEVED OOCYTES

Ottolina Jessica, Papaleo Enrico, Viganò Paola, Brigante Claudio, MarsiglioElena, De Michele Francesca, Candiani MassimoCentro Scienze Natalità, Obstetrics and Gynecology Unit, San RaffaeleScientific Institute, Milan, Italy

Introduction: Endometriosis-associated infertility is known to result inreduced ovarian response, fewer oocytes being available for fertilization