Dr. Burak Hacıhanefioğlu
polikistikover.net internet sitesinde yer alan tıp içerikli yazı ve videoların tümü Kadın Hastalıkları ve Doğum Uzmanı Dr. Burak Hacıhanefioğlu tarafından hazırlanmış olup, telif hakları yasal koruma altına alınmıştır. İzinsiz kaynak gösterilerek dahi başka bir yerde yayınlanamaz.
Gerçekten uygulanması gereken durumlar olan ileri derecede sperm bozukluğu ve her iki tüpünde tıkalı olması dışında polikistik over sendromu olanlarda tüp bebek uygulanması doğru değildir.
Polikistik over sendromu olan ve çocuk sahibi olmak isteyen kadınlara çeşitli nedenlerle ”senin çocuğun olmaz, sen kısırsın” veya ”tüp bebek yapılmasından başka çaren yok” deniliyor. Halbuki, tam tersine polikistik over sendromu olan kadınların yumurtalık rezervleri ve üreme kapasiteleri teorik olarak diğer kadınlardan daha fazladır(1,2,3,4,5,6,7,8). Polikistik over sendromu olan kadınların yarısından fazlası gebeliği engelleyen başka bir neden yoksa herhangi bir tedaviye ihtiyaç duymadan gebe kalabilmektedir(44). Hatta, gerek olmadığı halde yapılan tüp bebek tedavisi ile gebe kalamayanların bir kısmı da kendiliğinden bir süre sonra gebe kalmaktadır(49,50,51,52,53,54). Polikistik over sendromu olanların sadece bir kısmı yumurta gelişimi ve yumurtlama olmaması veya gecikmeli olması nedeniyle gebe kalmakta zorluk yaşamaktadır. (1,2,3,4,5,6,7,8,9).
Polikistik over sendromu nedeniyle gebe kalmakta zorluk yaşayanlara tüp bebek tedavisi yapılmasına gerek yoktur(10,11,12,13,14,15,16,17,18,19,20,21,22). Tüp bebek tedavisinin yenidoğan bebekte ve daha sonraki gelişim dönemlerinde otizm (autism) gibi yan etkilere neden olduğu son zamanlarda anlaşılmıştır. Genlerin etkinliğinin (expression) değişmesi (DNA methylation) (epigenetics) sonucunda otizm ortaya çıkmaktadır. (23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43). Bu nedenle gerçekten uygulanması gereken durumlar olan ileri derecede sperm bozukluğu ve her iki tüpünde (fallop tüpleri) tıkalı olması nedenleri dışında polikistik over sendromu olanlarda tüp bebek uygulanması doğru değildir. Halbuki, polikistik over sendromu nedeniyle gebe kalmakta zorluk yaşayan kadınlar çok daha zararsız, kolay uygulanan ve az masraflı tıbbi yöntemlerle zaten çocuk sahibi olabilmektedir. (10,11,12,13,14,15,16,17,18,19,20,21,22).
Polikistik over sendromu nedeniyle çocuk isteği tedavisine yeni başlayan yaklaşık 5 kadından birinin eşinin sperm sayısında ve hareketinde azlık veya şeklinde bozukluk görülürken, bu kadınların bir kısmının da tüplerinden birinin ya da her ikisinin tıkalı olduğu saptanmaktadır(45,46,47,48). Bu nedenle çocuk isteği tedavisine başlamadan önce polikistik over sendromu ile birlikte, sperm ile ilgili ve sperm ile yumurtanın birleştiği yer olan tüplerin (fallop tüpleri) bütünlüğünün bozulmasından kaynaklanan sorunların olup olmadığının belirlenmesi gerekmektedir(45,46). Ancak, polikistik over sendromu’na ek olarak sperm ve tüplerle ilgili sorunların da olması durumunda tüp bebek tedavisi düşünülmelidir.
Kaynaklar
1-Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called “hyperthecosis”. Hughesdon PE. Obstet Gynecol Surv. 1982 Feb;37(2):59-77.
2-Abnormal preantral folliculogenesis in polycystic ovaries is associated with increased granulosa cell division. Stubbs SA, Stark J, Dilworth SM, Franks S, Hardy K. J Clin Endocrinol Metab. 2007 Nov;92(11):4418-26.
3-Prolonged survival in culture of preantral follicles from polycystic ovaries. Webber LJ, Stubbs SA, Stark J, Margara RA, Trew GH, Lavery SA, Hardy K, Franks S. J Clin Endocrinol Metab. 2007 May;92(5):1975-8.
4-Formation and early development of follicles in the polycystic ovary. Webber LJ, Stubbs S, Stark J, Trew GH, Margara R, Hardy K, Franks S. Lancet. 2003 Sep 27;362(9389):1017-21.
5-Granulosa cells of polycystic ovaries: are they normal or abnormal? Erickson GF, Magoffin DA, Garzo VG, Cheung AP, Chang RJ. Hum Reprod. 1992 Mar;7(3):293-9.
6-Estradiol production by granulosa cells of normal and polycystic ovaries: relationship to menstrual cycle history and concentrations of gonadotropins and sex steroids in follicular fluid. Mason HD, Willis DS, Beard RW, Winston RM, Margara R, Franks S. J Clin Endocrinol Metab. 1994 Nov;79(5):1355-60.
7-Premature response to luteinizing hormone of granulosa cells from anovulatory women with polycystic ovary syndrome: relevance to mechanism of anovulation. Willis DS, Watson H, Mason HD, Galea R, Brincat M, Franks S. J Clin Endocrinol Metab. 1998 Nov;83(11):3984-91.
8-Etiology of anovulation in polycystic ovary syndrome. Franks S, Mason H, White D, Willis D. Steroids. 1998 May-Jun;63(5-6):306-7.
9-Nutrition, insulin and polycystic ovary syndrome. Franks S, Robinson S, Willis DS. Rev Reprod. 1996 Jan;1(1):47-53.
10-Intrauterine insemination: a UK survey on the adherence to NICE clinical guidelines by fertility clinics. Kim D, Child T, Farquhar C. BMJ Open. 2015 May 15;5(5):e007588.
11-Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial. Farquhar CM, Liu E, Armstrong S, Arroll N, Lensen S, Brown J. Lancet. 2018 Feb 3;391(10119):441-450.
12-Prevention of multiple pregnancies in couples with unexplained or mild male subfertility: randomised controlled trial of in vitro fertilisation with single embryo transfer or in vitro fertilisation in modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation. Bensdorp AJ, Tjon-Kon-Fat RI, et al. BMJ. 2015 Jan 9;350:g7771.
13-Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation? Tjon-Kon-Fat RI, Bensdorp AJ, et al. Hum Reprod. 2015 Oct;30(10):2331-9.
14-IUI: review and systematic assessment of the evidence that supports global recommendations. Cohlen B, Bijkerk A, Van der Poel S, Ombelet W. Hum Reprod Update. 2018 May 1;24(3):300-319.
15-Low-dose FSH therapy for anovulatory infertility associated with polycystic ovary syndrome: rationale, results, reflections and refinements. Homburg R, Howles CM. Hum Reprod Update. 1999 Sep-Oct;5(5):493-9.
16-High singleton live birth rate confirmed after ovulation induction in women with anovulatory polycystic ovary syndrome: validation of a prediction model for clinical practice. Veltman-Verhulst SM, Fauser BC, Eijkemans MJ. Fertil Steril. 2012 Sep;98(3):761-768.e1.
17-PCOS and pregnancy: a review of available therapies to improve the outcome of pregnancy in women with polycystic ovary syndrome. Artini PG, Obino MER, Sergiampietri C, Pinelli S, Papini F, Casarosa E, Cela V. Expert Rev Endocrinol Metab. 2018 Mar;13(2):87-98.
18-Clomiphene citrate and intrauterine insemination: analysis of more than 4100 cycles. Dovey S, Sneeringer RM, Penzias AS. Fertil Steril. 2008 Dec;90(6):2281-6.
19-Factors affecting the pregnancy rate in clomiphene citrate induction of ovulation. Hammond MG, Halme JK, Talbert LM. Obstet Gynecol. 1983 Aug;62(2):196-202.
20-Clomiphene citrate–end of an era? A mini-review. Homburg R. Hum Reprod. 2005 Aug;20(8):2043-51.
21-Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome. Amer SA, Smith J, Mahran A, Fox P, Fakis A. Hum Reprod. 2017 Aug 1;32(8):1631-1638.
22-Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. Wang R, Kim BV, van Wely M, Johnson NP, Costello MF, Zhang H, Ng EH, Legro RS, Bhattacharya S, Norman RJ, Mol BW. BMJ. 2017 Jan 31;356:j138.
23-Intracytoplasmic sperm injection and fetal origins of autism spectrum disorder: an intriguing, though controversial association. Briana DD, Malamitsi-Puchner A. J Matern Fetal Neonatal Med. 2020 Feb 20:1-7.
24-DNA methylation differences between in vitro- and in vivo-conceived children are associated with ART procedures rather than infertility. Song S, Ghosh J, Mainigi M, Turan N, Weinerman R, Truongcao M, Coutifaris C, Sapienza C. Clin Epigenetics. 2015 Apr 8;7(1):41.
25-Infertility Treatments and Long-Term Neurologic Morbidity of the Offspring. Levin S, Sheiner E, Wainstock T, Walfisch A, Segal I, Landau D, Sergienko R, Levitas E, Harlev A. Am J Perinatol. 2019 Jul;36(9):949-954.
26-DNA methylation and gene expression differences in children conceived in vitro or in vivo. Katari S, Turan N, Bibikova M, Erinle O, Chalian R, Foster M, Gaughan JP, Coutifaris C, Sapienza C. Hum Mol Genet. 2009 Oct 15;18(20):3769-78.
27-Are imprinting disorders more prevalent after human in vitro fertilization or intracytoplasmic sperm injection? Vermeiden JP, Bernardus RE. Fertil Steril. 2013 Mar 1;99(3):642-51.
28-Embryo manipulation and imprinting. Marchesi DE, Qiao J, Feng HL. Semin Reprod Med. 2012 Aug;30(4):323-34.
29-A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously. Lazaraviciute G, Kauser M, Bhattacharya S, Haggarty P, Bhattacharya S. Hum Reprod Update. 2014 Nov-Dec;20(6):840-52.
30-Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children. Kissin DM, Zhang Y, Boulet SL, Fountain C, Bearman P, Schieve L, Yeargin-Allsopp M, Jamieson DJ. Hum Reprod. 2015 Feb;30(2):454-65.
31-Genetic and epigenetic risks of assisted reproduction. Jiang Z, Wang Y, Lin J, Xu J, Ding G, Huang H. Best Pract Res Clin Obstet Gynaecol. 2017 Oct;44:90-104.
32-Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report. ESHRE Capri Workshop Group. J Assist Reprod Genet. 2014 Aug;31(8):947-58.
33-The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception: ART versus spontaneous conception without underlying infertility. Choux C, Binquet C, Carmignac V, Bruno C, Chapusot C, Barberet J, Lamotte M, Sagot P, Bourc’his D, Fauque P. Hum Reprod. 2018 Feb 1;33(2):331-340.
34-Association of birth defects with the mode of assisted reproductive technology in a Chinese data-linkage cohort. Yu HT, Yang Q, Sun XX, Chen GW, Qian NS, Cai RZ, Guo HB, Wang CF. Fertil Steril. 2018 May;109(5):849-856.
35-CDC analysis of ICSI/autism: association is not causation.Barad DH, Kushnir VA, Albertini D, Gleicher N. Hum Reprod. 2015 Jul;30(7):1745-6.
36-Reply: CDC analysis of ICSI/autism: association is not causation. Kissin DM, Zhang Y, Boulet SL, Fountain C, Bearman P, Schieve L, Yeargin-Allsopp M, Jamieson DJ. Hum Reprod. 2015 Jul;30(7):1746. 132-Reassurance from Sweden about autism and IVF. BMJ. 2013 Jul 3;347:f4239.
37-DNA methylation status of imprinted H19 and KvDMR1 genes in human placentas after conception using assisted reproductive technology. Chi F, Zhao M, Li K, Lin AQ, Li Y, Teng X. Ann Transl Med. 2020 Jul;8(14):854.
38-The hypomethylation of imprinted genes in IVF/ICSI placenta samples is associated with concomitant changes in histone modifications. Choux C, Petazzi P, Sanchez-Delgado M, Hernandez Mora JR, Monteagudo A, Sagot P, Monk D, Fauque P. Epigenetics. 2020 Dec;15(12):1386-1395.
39-Conception by fertility treatment and offspring deoxyribonucleic acid methylation. Yeung EH, Mendola P, Sundaram R, Zeng X, Guan W, Tsai MY, Robinson SL, Stern JE, Ghassabian A, Lawrence D, O’Connor TG, Segars J, Gore-Langton RE, Bell EM. Fertil Steril. 2021 Apr 3:S0015-0282(21)00216-8.
40-Time to re-evaluate ART protocols in the light of advances in knowledge about methylation and epigenetics: an opinion paper. Menezo Y, Dale B, Elder K. Hum Fertil (Camb). 2018 Sep;21(3):156-162.
41-DNA methylation differences at birth after conception through ART. Tobi EW, Almqvist C, Hedman A, Andolf E, Holte J, Olofsson JI, Wramsby H, Wramsby M, Pershagen G, Heijmans BT, Iliadou AN. Hum Reprod. 2021 Jan 1;36(1):248-259.
42-Do assisted reproductive technologies and in vitro embryo culture influence the epigenetic control of imprinted genes and transposable elements in children? Barberet J, Binquet C, Guilleman M, Doukani A, Choux C, Bruno C, Bourredjem A, Chapusot C, Bourc’his D, Duffourd Y, Fauque P. Hum Reprod. 2021 Jan 25;36(2):479-492.
43-Methylation: An Ineluctable Biochemical and Physiological Process Essential to the Transmission of Life. Menezo Y, Clement P, Clement A, Elder K. Int J Mol Sci. 2020 Dec 7;21(23):9311.
44-Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. Teede H, Deeks A, Moran L. BMC Med. 2010 Jun 30;8:41.
45-Utility of screening for other causes of infertility in women with “known” polycystic ovary syndrome. McGovern PG, Legro RS, Myers ER, Barnhart HX, Carson SA, Diamond MP, Carr BR, Schlaff WD, Coutifaris C, Steinkampf MP, Nestler JE, Gosman G, Leppert PC, Giudice LC; National Institutes for Child Health and Human Development-Reproductive Medicine Network. Fertil Steril. 2007 Feb;87(2):442-4.
46-The basic fertility workup in women with polycystic ovary syndrome: a systematic review. Nahuis MJ, Oosterhuis GJ, Hompes PG, van Wely M, Mol BW, van der Veen F. Fertil Steril. 2013 Jul;100(1):219-25.
47-The male factor in fertility and infertility. IV. Sperm morphology in fertile and infertile marriage. MacLEOD J, GOLD RZ. Fertil Steril. 1951 Sep-Oct;2(5):394-414.
48-The male factor in fertility and infertility. III. An analysis of motile activity in the spermatozoa of 1000 fertile men and 1000 men in infertile marriage. MACLEOD J, GOLD RZ. Fertil Steril. 1951 May-Jun;2(3):187-204.
49-Spontaneous pregnancies among couples previously treated by in vitro fertilization. Troude P, Bailly E, Guibert J, Bouyer J, de la Rochebrochard E; DAIFI Group. Fertil Steril. 2012 Jul;98(1):63-8.
50-The long-term outcome of 946 consecutive couples visiting a fertility clinic in 2001-2003. Donckers J, Evers JL, Land JA. Fertil Steril. 2011 Jul;96(1):160-4.
51-Spontaneous conceptions within two years of having a first infant with assisted conception. Wynter K, McMahon C, Hammarberg K, McBain J, Boivin J, Gibson F, Fisher J. Aust N Z J Obstet Gynaecol. 2013 Oct;53(5):471-6.
52-Live birth outcome, spontaneous pregnancy and adoption up to five years after undergoing assisted reproductive technology treatment. Volgsten H, Schmidt L. Acta Obstet Gynecol Scand. 2017 Aug;96(8):954-959.
53-Spontaneous conceptions following successful ART are not associated with premature referral. Lande Y, Seidman DS, Maman E, Baum M, Dor J, Hourvitz A. Hum Reprod. 2012 Aug;27(8):2380-3.
54-Outcome of assisted reproductive technology (ART) and subsequent self-reported life satisfaction. Kuivasaari-Pirinen P, Koivumaa-Honkanen H, Hippeläinen M, Raatikainen K, Heinonen S. PLoS One. 2014 Nov 13;9(11):e112540.