Fertility and Pregnancy in End Stage Kidney Failure Patients and after Renal Transplantation: An Update
Abstract
:1. Introduction
2. Fertility Disorders in Men with ESKD
3. Fertility Disorders in Women with ESKD
3.1. Female Sex Hormones
3.2. Menstrual Disorders
3.3. Endometrial Morphology
3.4. Ovarian Reserve
3.5. Reduced Libido and Sexual Dysfunction
4. Pregnancies and Deliveries in ESKD Women
5. Strategies to Improve Fertility in Women with CKD
- Avoidance of dangerous and ovarian-toxic drugs
- Improvement of dialysis strategy
- Kidney transplantation
6. Avoidance of Dangerous Drugs
7. Intensive HD
8. Kidney Transplantation
8.1. Sexual and Reproductive Health after Kidney Transplantation
8.2. Pregnancies after Kidney Transplantation
8.3. Renal Modifications during Pregnancy
8.4. Maternal Complications
8.5. Counseling
- -
- Discussion on sexual activity and counseling about contraception;
- -
- Recommend at least 1 year after transplantation before becoming pregnant;
- -
- Discuss the different immunosuppressive therapies and highlight which ones should be discontinued and replaced;
- -
- Counseling pregnant transplanted women on the risks and benefits of breastfeeding; and
- -
- Refer pregnant women to an obstetrician with expertise in managing high-risk pregnancies.
8.6. Timing of Conception, Mother Medical Condition before pregnancy, Follow-Up Recommended during Pregnancy
8.7. Immunosuppressive Agents
9. Corticosteroids
10. Calcineurine Inhibitors (CNI)
11. Azathioprine (AZA)
12. Mycophenolic Acid (MPA)
12.1. Sirolimus and Everolimus
12.2. Rituximab, Simulect, Belatacept
13. Pregnancies with Father Transplanted and Immunosuppressed
14. Deliveries in Kidney Transplant Women
15. Long-Term Outcomes for the Graft
16. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Holley, J.L.; Schmidt, R.J. Changes in Fertility and Hormone Replacement Therapy in Kidney Disease. Adv. Chronic Kidney Dis. 2013, 20, 240–245. [Google Scholar] [CrossRef] [PubMed]
- Rosas, S.E.; Joffe, M.; Franklin, E.; Strom, B.L.; Kotzker, W.; Brensinger, C.; Grossman, E.; Glasser, D.; Feldman, H. Prevalence and de-terminants of erectile dysfunction in hemodialysis patients. Kidney Int. 2001, 59, 2259–2266. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Türk, S.; Karalezli, G.; Tonbul, H.Z.; Yıldız, M.; Altıntepe, L.; Yıldız, A.; Yeksan, M. Erectile dysfunction and the effects of sildenafil treatment in patients on haemodialysis and continuous ambulatory peritoneal dialysis. Nephrol. Dial. Transplant. 2001, 16, 1818–1822. [Google Scholar] [CrossRef] [Green Version]
- Navaneethan, S.D.; Vecchio, M.; Johnson, D.W.; Saglimbene, V.; Graziano, G.; Pellegrini, F.; Lucisano, G.; Craig, J.C.; Ruospo, M.; Gentile, G.; et al. Prevalence and Correlates of Self-Reported Sexual Dysfunction in CKD: A Meta-analysis of Observational Studies. Am. J. Kidney Dis. 2010, 56, 670–685. [Google Scholar] [CrossRef]
- Billups, K.L. Erectile dysfunction as a marker for vascular disease. Curr. Urol. Rep. 2005, 6, 439–444. [Google Scholar] [CrossRef] [PubMed]
- Campese, V.M.; Procci, W.R.; Levitan, D.; Romoff, M.S.; A Goldstein, D.; Massry, S.G. Autonomic nervous system dysfunction and impotence in uremia. Am. J. Nephrol. 1982, 2, 213–220. [Google Scholar] [CrossRef]
- Holdsworth, S.R.; de Kretser, D.M.; Atkins, R.C. A comparison of hemodialysis and transplantation in reversing the uremic dis-turbance of male reproductive function. Clin. Nephrol. 1978, 10, 146–150. [Google Scholar]
- Reinhardt, W.; Kübber, H.; Dolff, S.; Benson, S.; Führer, D.; Tan, S. Rapid recovery of hypogonadism in male patients with end stage renal disease after renal transplantation. Endocrine 2018, 60, 159–166. [Google Scholar] [CrossRef]
- Carrero, J.J.; Qureshi, A.R.; Nakashima, A.; Arver, S.; Parini, P.; Lindholm, B.; Bárány, P.; Heimbürger, O.; Stenvinkel, P. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol. Dial. Transplant. 2011, 26, 184–190. [Google Scholar] [CrossRef] [Green Version]
- Holley, J.L. The hypothalamic-pituitary axis in men and women with chronic kidney disease. Adv. Chronic Kidney Dis. 2004, 11, 337–341. [Google Scholar] [CrossRef]
- Lim, V.S.; Fang, V.S. Restoration of plasma testosterone levels in uremic men with clomiphene citrate. J. Clin. Endocrinol. Metab. 1976, 43, 1370–1377. [Google Scholar] [CrossRef] [PubMed]
- Ayub, W.; Fletcher, S. End-stage renal disease and erectile dysfunction. Is there any hope? Nephrol. Dial. Transplant. 2000, 15, 1525–1528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Phocas, I.; Sarandakou, A.; Rizos, D.; Kapetanaki, A. Serum alpha-immunoreactive inhibin in males with renal failure, under haemodialysis and after successful renal transplantation. Andrologia 1995, 27, 253–258. [Google Scholar] [CrossRef] [PubMed]
- Isaac, R.; Merceron, R.E.; Caillens, G.; Raymond, J.-P.; Ardaillou, R. Effect of Parathyroid Hormone on Plasma Prolactin in Man. J. Clin. Endocrinol. Metab. 1978, 47, 18–23. [Google Scholar] [CrossRef]
- Lessan-Pezeshki, M.; Ghazizadeh, S. Sexual and reproductive function in end-stage renal disease and effect of kidney trans-plantation. Asian J. Androl. 2008, 10, 441–446. [Google Scholar] [CrossRef]
- Xu, L.-G.; Xu, H.-M.; Zhu, X.-F.; Jin, L.-M.; Xu, B.; Wu, Y.; Lu, N.-Q. Examination of the semen quality of patients with uraemia and renal transplant recipients in comparison with a control group. Andrologia 2009, 41, 235–240. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.M.; Li, H.G.; Xu, L.-G.; Zhang, J.-R.; Chen, W.-Y.; Shi, Q.-X. The decline of fertility in male uremic patients is correlated with low expression of the cystic fibrosis transmembrane conductance regulator protein (CFTR) in human sperm. Hum. Reprod. 2011, 27, 340–348. [Google Scholar] [CrossRef]
- Schaefer, F.; Van Kaick, B.; Veldhuis, J.D.; Stein, G.; Schärer, K.; Robertson, W.R.; Ritz, E. Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin. J. Am. Soc. Nephrol. 1994, 5, 1208–1215. [Google Scholar] [PubMed]
- Schaefer, R.M.; Kokot, F.; Wernze, H.; Geiger, H.; Heidland, A. Improved sexual function in hemodialysis patients on recombinant erythropoietin: A possible role for prolactin. Clin. Nephrol. 1989, 31, 1–5. [Google Scholar]
- Bellinghieri, G.; Santoro, D.; Lo Forti, B.; Mallamace, A.; De Santo, R.M.; Savica, V. Erectile dysfunction in uremic dialysis pa-tients: Diagnostic evaluation in the sildenafil era. Am. J. Kidney Dis. 2001, 38 (Suppl. 1), S115–S117. [Google Scholar] [CrossRef]
- Wiles, K.S.; Nelson-Piercy, C.; Bramham, K. Reproductive health and pregnancy in women with chronic kidney disease. Nat. Rev. Nephrol. 2018, 14, 165–184. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, S.B.; Ramesh, S. Sex hormones in women with kidney disease. Nephrol. Dial. Transplant. 2016, 31, 1787–1795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cochrane, R.; Regan, L. Undetected gynaecological disorders in women with renal disease. Hum. Reprod. 1997, 12, 667–670. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piccoli, G.B.; Cabiddu, G.; Daidone, G.; Guzzo, G.; Maxia, S.; Ciniglio, I.; Postorino, V.; Loi, V.; Ghiotto, S.; Nichelatti, M.; et al. The children of dialysis: Live-born babies from on-dialysis mothers in Italy--an epidemiological perspective comparing dialysis, kidney transplantation and the overall population. Nephrol. Dial. Transplant. 2014, 29, 1578–1586. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Knight, M.; Kurinczuk, J.J.; Tuffnell, D.; Brocklehurst, P. The UK Obstetric Surveillance System for rare disorders of pregnancy. BJOG 2005, 112, 263–265. [Google Scholar] [CrossRef]
- Statistical Bulletin: Conceptions in England and Wales 2015. Office for National Statistics. 2017. Available online: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/conceptionandfertilityrates/bulletins/conceptionstatistics/2015 (accessed on 20 August 2018).
- Ahmed, S.B.; Vitek, W.S.; Holley, J.L. Fertility, Contraception, and Novel Reproductive Technologies in Chronic Kidney Dis-ease. Semin. Nephrol. 2017, 37, 327–336. [Google Scholar] [CrossRef]
- Matuszkiewicz-Rowinska, J.; Skórzewska, K.; Radowicki, S.; Niemczyk, S.; Sokalski, A.; Przedlacki, J.; Puka, J.; Switalski, M.; Wardyn, K.; Grochowski, J.; et al. Endometrial morphology and pituitary-gonadal axis dysfunction in women of reproduc-tive age undergoing chronic haemodialysis—A multicentre study. Nephrol. Dial. Transplant. 2004, 19, 2074–2077. [Google Scholar] [CrossRef] [Green Version]
- Harlow, S.D.; Gass, M.; Hall, J.E.; Lobo, R.; Maki, P.; Rebar, R.W.; Sherman, S.; Sluss, P.M.; de Villiers, T.J.; STRAW+ 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: Addressing the unfinished agenda of staging re-productive aging. J. Clin. Endocrinol. Metab. 2012, 97, 1159–1168. [Google Scholar] [CrossRef]
- Rose, C.; Gill, J.; Zalunardo, N.; Johnston, O.; Mehrotra, A.; Gill, J.S. Timing of Pregnancy After Kidney Transplantation and Risk of Allograft Failure. Am. J. Transplant. 2016, 16, 2360–2367. [Google Scholar] [CrossRef] [Green Version]
- Filocamo, M.T.; Zanazzi, M.; Marzi, V.L.; Lombardi, G.; Del Popolo, G.; Mancini, G.; Salvadori, M.; Nicita, G. Sexual Dysfunction in Women During Dialysis and after Renal Transplantation. J. Sex. Med. 2009, 6, 3125–3131. [Google Scholar] [CrossRef]
- Barua, M.; Hladunewich, M.; Keunen, J.; Pierratos, A.; McFarlane, P.; Sood, M.; Chan, C.T. Successful Pregnancies on Nocturnal Home Hemodialysis. Clin. J. Am. Soc. Nephrol. 2008, 3, 392–396. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stoumpos, S.; Lees, J.; Welsh, P.; Hund, M.; Geddes, C.C.; Nelson, S.M.; Mark, P.B. The utility of anti-Müllerian hormone in women with chronic kidney disease, on haemodialysis and after kidney transplantation. Reprod. Biomed. Online 2018, 36, 219–226. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Holley, J.L.; Schmidt, R.J. Sexual dysfunction in CKD. Am. J. Kidney Dis. 2010, 56, 612–614. [Google Scholar] [CrossRef]
- Oliverio, A.L.; Bragg-Gresham, J.L.; Admon, L.K.; Nunes, J.A.W.; Saran, R.; Heung, M. Obstetric Deliveries in US Women With ESKD: 2002-2015. Am. J. Kidney Dis. 2020, 75, 762–771. [Google Scholar] [CrossRef] [PubMed]
- Shahir, A.K.; Briggs, N.; Katsoulis, J.; Levidiotis, V. An observational outcomes study from 1966–2008, examining pregnancy and neonatal outcomes from dialysed women using data from the ANZDATA Registry. Nephrology 2013, 18, 276–284. [Google Scholar] [CrossRef] [PubMed]
- Tong, A.; Jesudason, S.; Craig, J.C.; Winkelmayer, W.C. Perspectives on pregnancy in women with chronic kidney disease: Sys-tematic review of qualitative studies. Nephrol. Dial. Transplant. 2015, 30, 652–661. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leroy, C.; Rigot, J.M.; Leroy, M.; Decanter, C.; Le Mapihan, K.; Parent, A.S.; Le Guillou, A.C.; Yakoub-Agha, I.; Dharancy, S.; Noel, C.; et al. Immunosuppressive drugs and fertility. Orphanet J. Rare Dis. 2015, 10, 136–151. [Google Scholar] [CrossRef] [Green Version]
- Somers, E.C.; Marder, W.; Christman, G.M.; Ognenovski, V.; McCune, W.J. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum. 2005, 52, 2761–2767. [Google Scholar] [CrossRef]
- Lambertini, M.; Boni, L.; Michelotti, A.; Gamucci, T.; Scotto, T.; Gori, S.; Giordano, M.; Garrone, O.; Levaggi, A.; Poggio, F.; et al. Ovarian Suppression With Triptorelin During Adjuvant Breast Cancer Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial. JAMA 2015, 314, 2632–2640. [Google Scholar] [CrossRef] [Green Version]
- Hladunewich, M.; Schatell, D. Intensive dialysis and pregnancy. Hemodial. Int. 2016, 20, 339–348. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Van Eps, C.; Hawley, C.; Jeffries, J.; Johnson, D.W.; Campbell, S.; Isbel, N.; Mudge, D.W.; Prins, J. Changes in serum prolactin, sex hormones and thyroid function with alternate nightly nocturnal home haemodialysis. Nephrology 2012, 17, 42–47. [Google Scholar] [CrossRef]
- Piccoli, G.B.; Minelli, F.; Versino, E.; Cabiddu, G.; Attini, R.; Vigotti, F.N.; Rolfo, A.; Giuffrida, D.; Colombi, N.; Pani, A.; et al. Pregnancy in dialysis patients in the new millennium: A systematic review and meta-regression analysis correlating dialysis schedules and pregnancy outcomes. Nephrol. Dial. Transplant. 2016, 31, 1915–1934. [Google Scholar] [CrossRef]
- Wiles, K.; Chappell, L.; Clark, K.; Elman, L.; Hall, M.; Lightstone, L.; Mohamed, G.; Mukherjee, D.; Nelson-Piercy, C.; Webster, P.; et al. Clinical practice guideline on pregnancy and renal disease. BMC Nephrol. 2019, 20, 401. [Google Scholar] [CrossRef] [Green Version]
- Pietrzak, B.; Wielgos, M.; Kaminski, P.; Jabiry-Zieniewicz, Z.; Bobrowska, K. Menstrual cycle and sex hormone profile in kid-ney-transplanted women. Neuro Endocrinol. Lett. 2006, 27, 198–202. [Google Scholar]
- Chakhtoura, Z.; Meunier, M.; Caby, J.; Mercadal, L.; Arzouk, N.; Barrou, B.; Touraine, P. Gynecologic follow up of 129 women on dialysis and after kidney transplantation: A retrospective cohort study. Eur. J. Obstet. Gynecol. Reprod. Biol. 2015, 187, 1–5. [Google Scholar] [CrossRef]
- Akbari, F.; Alavi, M.; Esteghamati, A.; Mehrsai, A.; Djaladat, H.; Zohrevand, R.; Pourmand, G. Effect of renal transplantation on sperm quality and sex hormone levels. BJU Int. 2003, 92, 281–283. [Google Scholar] [CrossRef]
- Tainio, J.; Jahnukainen, K.; Nurmio, M.; Pakarinen, M.; Jalanko, H.; Jahnukainen, T. Testicular function, semen quality, and fertili-ty in young men after renal transplantation during childhood or adolescence. Transplantation 2014, 98, 987–993. [Google Scholar] [CrossRef] [PubMed]
- Eckersten, D.; Giwercman, A.; Pihlsgård, M.; Bruun, L.; Christensson, A. Impact of Kidney Transplantation on Reproductive Hormone Levels in Males: A Longitudinal Study. Nephron 2017, 138, 192–201. [Google Scholar] [CrossRef] [PubMed]
- Prem, A.R.; Punekar, S.V.; Kalpana, M.; Kelkar, A.R.; Acharya, V.N. Male reproductive function in uraemia: Efficacy of haemodi-alysis and renal transplantation. Br. J. Urol. 1996, 78, 635–638. [Google Scholar] [CrossRef] [PubMed]
- Rodrigues Netto, N., Jr.; Pecoraro, G.; Sabbaga, E.; Menezes de Góes, G. Spermatogenesis before and after renal transplant. Int. J. Fertil. 1980, 25, 131–133. [Google Scholar] [PubMed]
- Eid, M.M.; Sobh, M.A.; Abdel-Hamid, I.A.; El-Saied, M.A. Assessment of sperm motion characteristics in infertile renal transplant recipients using computerized analysis. Int. J. Androl. 1996, 19, 338–344. [Google Scholar] [CrossRef]
- Diemont, W.L.; Vruggink, P.A.; Meuleman, E.J.; Doesburg, W.H.; Lemmens, W.A.; Berden, J.H. Sexual dysfunction after renal re-placement therapy. Am. J. Kidney Dis. 2000, 35, 845–851. [Google Scholar] [CrossRef]
- Stehman-Breen, C.O.; Gillen, D.; Gipson, D. Prescription of hormone replacement therapy in postmenopausal women with renal failure. Kidney Int. 1999, 56, 2243–2247. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lawrence, I.G.; Price, D.E.; Howlett, T.A.; Harris, K.P.; Feehally, J.; Walls, J. Correcting impotence in the male dialysis patient: Expe-rience with testosterone replacement and vacuum tumescence therapy. Am. J. Kidney Dis. 1998, 31, 313–319. [Google Scholar] [CrossRef] [PubMed]
- Murray, J.E.; Reid, D.E.; Harrison, J.H.; Merrill, J.P. Successful Pregnancies after Human Renal Transplantation. N. Engl. J. Med. 1963, 269, 341–343. [Google Scholar] [CrossRef] [PubMed]
- Deshpande, N.A.; James, N.T.; Kucirka, L.M.; Boyarsky, B.J.; Garonzik-Wang, J.M.; Montgomery, R.A.; Segev, D.L. Pregnancy out-comes in kidney transplant recipients: A systematic review and meta-analysis. Am. J. Transplant. 2011, 11, 2388–2404. [Google Scholar] [CrossRef]
- Gill, J.S.; Zalunardo, N.; Rose, C.; Tonelli, M. The Pregnancy Rate and Live Birth Rate in Kidney Transplant Recipients. Arab. Archaeol. Epigr. 2009, 9, 1541–1549. [Google Scholar] [CrossRef]
- Transplant Pregnancy Registry International (TPR). Annual Report 2017; Gift of Life Institute: Philadelphia, PA, USA, 2018. [Google Scholar]
- Van Buren, M.C.; Schellekens, A.; Groenhof, T.K.J.; van Reekum, F.; van de Wetering, J.; Paauw, N.D.; Lely, A.T. Long-term Graft Sur-vival and Graft Function Following Pregnancy in Kidney Transplant Recipients: A Systematic Review and Meta-analysis. Transplantation 2020, 104, 1675–1685. [Google Scholar] [CrossRef]
- Sibanda, N.; Briggs, J.D.; Davison, J.M.; Johnson, R.J.; Rudge, C.J. Pregnancy after Organ Transplantation: A Report from the U.K. Transplant Pregnancy Registry. Transplantation 2007, 83, 1301–1307. [Google Scholar] [CrossRef]
- Díaz, J.M.; Canal, C.; Giménez, I.; Guirado, L.; Facundo, C.; Solà, R.; Ballarín, J. Pregnancy in recipients of kidney transplantation: Effects on mother and child. Nefrología 2008, 28, 174–177. [Google Scholar]
- Rao, S.; Ghanta, M.; Moritz, M.J.; Constantinescu, S. Long-Term Functional Recovery, Quality of Life, and Pregnancy After Solid Organ Transplantation. Med. Clin. N. Am. 2016, 100, 613–629. [Google Scholar] [CrossRef]
- Mastrosimone, S.; Pignata, G.; Maresca, M.C.; Calconi, G.; Rabassini, A.; Butini, R.; Fandella, A.; Di Falco, G.; Chiara, G.; Caldato, C. Clinical significance of vesicoureteral reflux after kidney transplantation. Clin. Nephrol. 1993, 40, 38–45. [Google Scholar]
- Ajaimy, M.; Lubetzky, M.; Jones, T.; Kamal, L.; Colovai, A.; De Boccardo, G.; Akalin, E. Pregnancy in sensitized kidney transplant recipients: A single center experience. Clin. Transplant. 2016, 30, 791–795. [Google Scholar] [CrossRef]
- Richman, K.; Gohh, R.; Peters, H.P.; Rumjon, A.; Bansal, S.S.; Laarakkers, C.M.; Brand, J.A.V.D.; Sarafidis, P.; Musto, R.; Malyszko, J.; et al. Pregnancy after renal transplantation: A review of registry and single-center practices and outcomes. Nephrol. Dial. Transplant. 2012, 27, 3428–3434. [Google Scholar] [CrossRef] [Green Version]
- Deshpande, N.A.; James, N.T.; Kucirka, L.M.; Boyarsky, B.J.; Garonzik-Wang, J.M.; Cameron, A.M.; Singer, A.L.; Dagher, N.N.; Segev, D.L. Pregnancy outcomes of liver transplant recipients: A systematic review and meta-analysis. Liver Transplant. 2012, 18, 621–629. [Google Scholar] [CrossRef] [PubMed]
- Moritz, M.J.; Constantinescu, S.; Coscia, L.A.; Armenti, D.; Transplant Pregnancy Registry International (TPR). Annual Report 2016; Gift of Life Institute: Philadelphia, PA, USA, 2017; pp. 1–23. [Google Scholar]
- Coscia, L.A.; Constantinescu, S.; Moritz, M.J.; Frank, A.M.; Ramirez, C.B.; Doria, C.; McGrory, C.H.; Armenti, V.T. Report from the National Transplantation Pregnancy Registry (NTPR): Outcomes of pregnancy after transplantation. Clin. Transpl. 2008, 89–105, Chapter 8. [Google Scholar]
- A Magee, L.; Von Dadelszen, P.; Darley, J.; Beguin, Y. Erythropoiesis and renal transplant pregnancy. Clin. Transplant. 2000, 14, 127–135. [Google Scholar] [CrossRef] [Green Version]
- Sarkar, M.; Bramham, K.; Moritz, M.J.; Coscia, L. Reproductive health in women following abdominal organ transplant. Arab. Archaeol. Epigr. 2018, 18, 1068–1076. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Westbrook, R.H.; Yeoman, A.D.; Agarwal, K.; Aluvihare, V.; O’Grady, J.; Heaton, N.; Penna, L.; Heneghan, M.A. Outcomes of pregnancy following liver transplantation: The King’s College Hospital experience. Liver Transpl. 2015, 21, 1153–1159. [Google Scholar] [CrossRef] [PubMed]
- Yildirim, Y.; Uslu, A. Pregnancy in patients with previous successful renal transplantation. Int. J. Gynecol. Obstet. 2005, 90, 198–202. [Google Scholar] [CrossRef] [PubMed]
- Rafie, S.; Lai, S.; Garcia, J.E.; Mody, S.K. Contraceptive Use in Female Recipients of a Solid-Organ Transplant. Prog. Transplant. 2014, 24, 344–348. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, L.; Yang, Y.; Shi, J.G.; Wang, H.; Qiu, F.; Peng, W.; Fu, J.; Zhu, X.; Zhu, Y. Unwanted pregnancy among Chinese renal transplant recipients. Eur. J. Contracept. Reprod. Health Care 2011, 16, 270–276. [Google Scholar] [CrossRef] [PubMed]
- Bramham, K.; Nelson-Piercy, C.; Gao, H.; Pierce, M.; Bush, N.; Spark, P.; Brocklehurst, P.; Kurinczuk, J.J.; Knight, M. Pregnancy in Renal Transplant Recipients: A UK National Cohort Study. Clin. J. Am. Soc. Nephrol. 2012, 8, 290–298. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kasiske, B.L.; Zeier, M.G.; Chapman, J.R.; Craig, J.C.; Ekberg, H.; Garvey, C.A.; Green, M.D.; Jha, V.; Josephson, M.A.; Kiberd, B.A.; et al. KDIGO clinical practice guideline for the care of kidney transplant recipients: A summary. Kidney Int. 2010, 77, 299–311. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piccoli, G.B.; Cabiddu, G.; Attini, R.; Vigotti, F.N.; Maxia, S.; Lepori, N.; Tuveri, M.; Massidda, M.; Marchi, C.; Mura, S.; et al. Risk of Adverse Pregnancy Outcomes in Women with CKD. J. Am. Soc. Nephrol. 2015, 26, 2011–2022. [Google Scholar] [CrossRef] [Green Version]
- You, J.Y.; Kim, M.-K.; Choi, S.-J.; Oh, S.-Y.; Kim, S.-J.; Kim, J.-H.; Oh, H.-Y.; Roh, C.-R. Predictive factors for adverse pregnancy outcomes after renal transplantation. Clin. Transplant. 2014, 28, 699–706. [Google Scholar] [CrossRef]
- Davison, J.M.; Lindheimer, M.D. Pregnancy and Chronic Kidney Disease. Semin. Nephrol. 2011, 31, 86–99. [Google Scholar] [CrossRef]
- Piccoli, G.B.; Cabiddu, G.; Attini, R.; Gerbino, M.; Todeschini, P.; Perrino, M.L.; Manzione, A.M.; Piredda, G.B.; Gnappi, E.; Caputo, F.; et al. Outcomes of Pregnancies After Kidney Transplantation: Lessons Learned From CKD. A Comparison of Transplanted, Nontransplanted Chronic Kidney Disease Patients and Low-Risk Pregnancies: A Multicenter Nationwide Analysis. Transplantation 2017, 101, 2536–2544. [Google Scholar] [CrossRef]
- McKay, D.B.; Josephson, M.A.; Armenti, V.T.; August, P.; Coscia, L.A.; Davis, C.L.; Davison, J.M.; Easterling, T.; Friedman, J.E.; Hou, S.; et al. Reproduction and transplantation: Report on the AST Consensus Conference on Reproductive Issues and Transplantation. Am. J. Transplant. 2005, 5, 1592–1599. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cabiddu, G.; Spotti, D.; Gernone, G.; Santoro, D.; Moroni, G.; Gregorini, G.; Giacchino, F.; Attini, R.; Limardo, M.; Gammaro, L.; et al. A best-practice position statement on pregnancy after kidney transplantation: Focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology. J. Nephrol. 2018, 31, 665–681. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McKay, D.B.; Josephson, M.A. Pregnancy in Recipients of Solid Organs—Effects on Mother and Child. N. Engl. J. Med. 2006, 354, 1281–1293. [Google Scholar] [CrossRef] [Green Version]
- Levitz, M.; Jansen, V.; Dancis, J. The transfer and metabolism of corticosteroids in the perfused human placenta. Am. J. Obstet. Gynecol. 1978, 132, 363–366. [Google Scholar] [CrossRef]
- Carmichael, S.L.; Shaw, G.M.; Ma, C.; Werler, M.M.; Rasmussen, S.A.; Lammer, E.J. National Birth Defects Prevention Study. Maternal corticosteroid use and orofacial clefts. Am. J. Obstet. Gynecol. 2007, 197, 585.e1–585.e7. [Google Scholar] [CrossRef]
- Hebert, M.F.; Zheng, S.; Hays, K.; Shen, D.D.; Davis, C.L.; Umans, J.G.; Miodovnik, M.; Thummel, K.E.; Easterling, T.R. Interpreting Tacrolimus Concentrations During Pregnancy and Postpartum. Transplantation 2013, 95, 908–915. [Google Scholar] [CrossRef] [Green Version]
- Mason, R.J.; Thomson, A.W.; Whiting, P.H.; Gray, E.S.; A Brown, P.; Catto, G.R.; Simpson, J.G. Cyclosporine-induced fetotoxicity in the rat. Transplantation 1985, 39, 9–12. [Google Scholar]
- Paziana, K.; Del Monaco, M.; Cardonick, E.; Moritz, M.; Keller, M.; Smith, B.; Coscia, L.; Armenti, V. Ciclosporin Use During Pregnancy. Drug Saf. 2013, 36, 279–294. [Google Scholar] [CrossRef]
- EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol. Dial. Transplant. 2002, 17 (Suppl. 4), 50–55. [Google Scholar]
- Hoeltzenbein, M.; Elefant, E.; Vial, T.; Finkel-Pekarsky, V.; Stephens, S.; Clementi, M.; Allignol, A.; Weber-Schoendorfer, C.; Schaefer, C. Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. Am. J. Med. Genet. Part A 2012, 158, 588–596. [Google Scholar] [CrossRef] [PubMed]
- Moritz, M.J.; Constantinescu, S.; Coscia, L.A.; Armenti, D. Mycophenolate and Pregnancy: Teratology Principles and National Transplantation Pregnancy Registry Experience. Arab. Archaeol. Epigr. 2017, 17, 581–582. [Google Scholar] [CrossRef] [PubMed]
- King, R.W.; Baca, M.J.; Armenti, V.T.; Kaplan, B. Pregnancy Outcomes Related to Mycophenolate Exposure in Female Kidney Transplant Recipients. Arab. Archaeol. Epigr. 2016, 17, 151–160. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Constantinescu, S.; Coscia, L.A.; Armenti, V.T. Mycophenolic acid product discontinuation prior to conception: Analysis of pregnancies in kidney transplant recipients. Am. J. Transplant. 2016, 16, 228. [Google Scholar]
- Braun, M.; Young, J.; Reiner, C.S.; Poster, D.; Krauer, F.; Kistler, A.D.; Kristanto, P.; Wang, X.; Liu, Y.; Loffing, J.; et al. Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: Analysis of the randomized controlled SUISSE ADPKD trial. PLoS ONE 2012, 7, e45868. [Google Scholar] [CrossRef]
- Carta, P.; Caroti, L.; Zanazzi, M. Pregnancy in a Kidney Transplant Patient Treated With Everolimus. Am. J. Kidney Dis. 2012, 60, 329. [Google Scholar] [CrossRef] [PubMed]
- Pendergraft, W.F., 3rd; McGrath, M.M.; Murphy, A.P.; Murphy, P.; Laliberte, K.A.; Greene, M.F.; Niles, J.L. Fetal outcomes after rituxi-mab exposure in women with autoimmune vasculitis. Ann. Rheum. Dis. 2013, 72, 2051–2053. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, L.; Wang, H.; Peng, W.; Jin, L.; Zhu, X.; Xu, H.; Song, Q.; Xu, B.; Ding, X. Marital Status and Fertility of 185 Male Renal Transplant Recipients in China. J. Androl. 2008, 29, 618–621. [Google Scholar] [CrossRef] [PubMed]
- Jones, A.; Clary, M.J.; McDermott, E.; Coscia, L.A.; Constantinescu, S.; Moritz, M.J.; Armenti, V.T. Outcomes of Pregnancies Fathered by Solid-Organ Transplant Recipients Exposed to Mycophenolic Acid Products. Prog. Transplant. 2013, 23, 153–157. [Google Scholar] [CrossRef]
- Midtvedt, K.; Bergan, S.; Reisæter, A.V.; Vikse, B.E.; Åsberg, A. Exposure to Mycophenolate and Fatherhood. Transplantation 2017, 101, e214–e217. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tondolo, V.; Citterio, F.; Panocchia, N.; Nanni, G.; Castagneto, M. Sirolimus Impairs Improvement of the Gonadal Function after Renal Transplantation. Arab. Archaeol. Epigr. 2005, 5, 197. [Google Scholar] [CrossRef]
- Liu, S.; Huang, L.; Geng, Y.; He, J.; Chen, X.; Xuemei, C.; Junlin, H.; Wang, Y.; Ding, Y.; Liu, X. Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats. Mol. Med. Rep. 2017, 16, 4029–4037. [Google Scholar] [CrossRef] [Green Version]
- Zuber, J.; Anglicheau, D.; Elie, C.; Bererhi, L.; Timsit, M.O.; Mamzer-Bruneel, M.F.; Ciroldi, M.; Martinez, F.; Snanoudj, R.; Hiesse, C.; et al. Sirolimus may reduce fertility in male renal transplant recipients. Am. J. Transplant. 2008, 8, 1471–1479. [Google Scholar] [CrossRef]
- Lundy, S.D.; Vij, S.C. Male infertility in renal failure and transplantation. Transl. Androl. Urol. 2019, 8, 173–181. [Google Scholar] [CrossRef] [PubMed]
- Blume, C.; Pischke, S.; Von Versen-Höynck, F.; Günter, H.; Gross, M. Pregnancies in liver and kidney transplant recipients: A review of the current literature and recommendation. Best Pract. Res. Clin. Obstet. Gynaecol. 2014, 28, 1123–1136. [Google Scholar] [CrossRef]
- Piccoli, G.B.; Cabiddu, G.; Attini, R.; Gerbino, M.; Todeschini, P.; Perrino, M.L.; Manzione, A.M.; Piredda, G.B.; Gnappi, E.; Caputo, F.; et al. Pregnancy outcomes after kidney graft in Italy: Are the changes over time the result of different therapies or of different policies? A nationwide survey (1978–2013). Nephrol. Dial. Transplant. 2016, 31, 1957–1965. [Google Scholar] [CrossRef]
- Parazzini, F.; Cortinovis, I.; Bortolus, R.; Soliani, A.; Fedele, L. Weight at birth of singleton live births between the 23rd and 27th week of gestation delivered vaginally or by cesarean section. Acta Paediatr. 1994, 83, 1206–1208. [Google Scholar] [CrossRef] [PubMed]
- Shah, S.; Venkatesan, R.L.; Gupta, A.; Sanghavi, M.K.; Welge, J.; Johansen, R.; Kean, E.B.; Kaur, T.; Gupta, A.; Grant, T.J.; et al. Pregnancy outcomes in women with kidney transplant: Metaanalysis and systematic review. BMC Nephrol. 2019, 20, 24. [Google Scholar] [CrossRef]
- Durst, J.K.; Rampersad, R.M. Pregnancy in Women with Solid-Organ Transplants: A Review. Obstet. Gynecol. Surv. 2015, 70, 408–418. [Google Scholar] [CrossRef]
- Sturgiss, S.; Davison, J. Effect of pregnancy on the long-term function of renal allografts: An update. Am. J. Kidney Dis. 1995, 26, 54–56. [Google Scholar] [CrossRef]
- Fischer, T.; Neumayer, H.-H.; Fischer, R.; Barenbrock, M.; Schobel, H.P.; Lattrell, B.C.; Jacobs, V.R.; Paepke, S.; Von Steinburg, S.P.; Schmalfeldt, B.; et al. Effect of Pregnancy on Long-Term Kidney Function in Renal Transplant Recipients Treated with Cyclosporine and with Azathioprine. Arab. Archaeol. Epigr. 2005, 5, 2732–2739. [Google Scholar] [CrossRef]
- First, M.R.; A Combs, C.; Weiskittel, P.; Miodovnik, M. Lack of effect of pregnancy on renal allograft survival or function. Transplantation 1995, 59, 472–476. [Google Scholar] [CrossRef]
- Candido, C.; Cristelli, M.P.; Fernandes, A.R.; De Lima, A.C.A.; Viana, L.A.; Sato, J.L.; Sass, N.; Tedesco-Silva, H.; Medina-Pestana, J.O. Pregnancy after kidney transplantation: High rates of maternal complications. Braz. J. Nephrol. 2016, 38, 421–426. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Keitel, E.; Bruno, R.; Duarte, M.; Santos, A.; Bittar, A.; Bianco, P.; Goldani, J.; Garcia, V. Pregnancy outcome after renal transplantation. Transplant. Proc. 2004, 36, 870–871. [Google Scholar] [CrossRef] [PubMed]
- Kwek, J.L.; Tey, V.; Yang, L.; Kanagalingam, D.; Kee, T. Renal and obstetric outcomes in pregnancy after kidney transplantation: Twelve-year experience in a Singapore transplant center. J. Obstet. Gynaecol. Res. 2015, 41, 1337–1344. [Google Scholar] [CrossRef] [PubMed]
- Levidiotis, V.; Chang, S.; McDonald, S. Pregnancy and Maternal Outcomes Among Kidney Transplant Recipients. J. Am. Soc. Nephrol. 2009, 20, 2433–2440. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rahamimov, R.; Ben-Haroush, A.; Wittenberg, C.; Mor, E.; Lustig, S.; Gafter, U.; Hod, M.; Bar, J. Pregnancy in renal transplant recipients: Long-term effect on patient and graft survival. A single-center experience. Transplantation 2006, 81, 660–664. [Google Scholar] [CrossRef] [PubMed]
Vascular System |
---|
|
Neurologic system |
|
Endocrine system |
|
Psychologic system |
Other factors |
|
Impaired Spermatogenesis |
---|
|
Testicular damage |
|
Impaired gonadal steroidogenesis |
|
Disruption of gonadotropin release |
|
Elevated prolactin |
|
Abnormal levels of sex hormones |
Menstrual disorders |
Abnormal endometrial morphology |
Reduced ovarian reserve |
Reduced libido and sexual dysfunction |
Drug | Usual Dosage Range | Animal Reproductive Data | FDA Pregnancy Category |
---|---|---|---|
Corticosteroids Prednisone Methylprednisolone | 5–20 mg/day 500–1000 mg/day (antirejection) | Yes Yes | C |
Azathioprine | 0.5–1.0 mg/kg/day | Yes | D |
Cyclosporine | 2–10 mg/kg/day | Yes | C |
Tacrolimus | 0.05–0.2 mg/kg/day | Yes | C |
Mycophenolate mofetil | 1000–2000 mg/day | Yes | D |
Mycophenolic acid | 720–1440 mg BID | Yes | D |
Sirolimus | 2–5 mg/day | Yes | C |
Everolimus | 5–10 mg/kg | Yes | C |
Hypertension before or during pregnancy |
Proteinuria before pregnancy |
Transplant to conception interval |
Pre-conception graft function |
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Salvadori, M.; Tsalouchos, A. Fertility and Pregnancy in End Stage Kidney Failure Patients and after Renal Transplantation: An Update. Transplantology 2021, 2, 92-108. https://doi.org/10.3390/transplantology2020010
Salvadori M, Tsalouchos A. Fertility and Pregnancy in End Stage Kidney Failure Patients and after Renal Transplantation: An Update. Transplantology. 2021; 2(2):92-108. https://doi.org/10.3390/transplantology2020010
Chicago/Turabian StyleSalvadori, Maurizio, and Aris Tsalouchos. 2021. "Fertility and Pregnancy in End Stage Kidney Failure Patients and after Renal Transplantation: An Update" Transplantology 2, no. 2: 92-108. https://doi.org/10.3390/transplantology2020010