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{{WikiDoc CMG}}; {{AE}} {{NS}}
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{{SK}}
{{SK}} Approach to Infertility, Approach to subfertility, Approach to impotence
 
{| class="infobox" style="margin: 0 0 0 0; border: 0; float: right; width: 100px; background: #A8A8A8; position: fixed; top: 250px; right: 21px; border-radius: 0 0 10px 10px;" cellpadding="0" cellspacing="0" ;
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! style="padding: 0 5px; font-size: 85%; background: #A8A8A8" align="center" |{{fontcolor|#2B3B44|Infertility Resident Survival Guide Microchapters}}
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align="left" |[[Infertility resident survival guide#Overview|Overview]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align="left" |[[Infertility resident survival guide#Causes|Causes]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align="left" |[[Infertility resident survival guide#Diagnosis|Diagnosis]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align="left" |[[Infertility resident survival guide#Treatment|Treatment]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align="left" |[[Infertility resident survival guide#Dos|Dos]]
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! style="font-size: 80%; padding: 0 5px; background: #DCDCDC" align="left" |[[Infertility resident survival guide#Don'ts|Don'ts]]
|}
 
 
==Overview==
==Overview==
[[Infertility]] is defined as a failure to conceive after one or more years of unprotected intercourse<ref name="pmid15802321">{{cite journal| author=Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G| title=Definition and prevalence of subfertility and infertility. | journal=Hum Reprod | year= 2005 | volume= 20 | issue= 5 | pages= 1144-7 | pmid=15802321 | doi=10.1093/humrep/deh870 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15802321  }} </ref>. Infertility is divided broadly into primary and secondary infertility where primary infertility is failure to conceive and secondary infertility is failure to conceive after a previous [[pregnancy]]. Multiple factors play a role in conception and infertility such as healthy [[spermatozoa]], regular [[ovulation]], patent [[fallopian tube]]s, normal [[uterine cavity]] etc.<ref name="pmid25604696">{{cite journal| author=Dadhich P, Ramasamy R, Lipshultz LI| title=The male infertility office visit. | journal=Minerva Urol Nefrol | year= 2015 | volume= 67 | issue= 2 | pages= 157-68 | pmid=25604696 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25604696  }} </ref>
[[Infertility]] is defined as a failure to conceive after one or more years of unprotected intercourse. Infertility is divided broadly into primary and secondary infertility where primary infertility is failure to conceive and secondary infertility is failure to conceive after a previous [[pregnancy]]. Multiple factors play a role in conception and infertility such as healthy [[spermatozoa]], regular [[ovulation]], patent [[fallopian tube]]s, normal [[uterine cavity]] etc.


==Causes==
==Causes==
Common causes of female infertility are listed below.
Common [[causes]] of female infertility are listed below.
===Genetic causes===
===Genetic causes===
* [[Turner's syndrome]]
 
* [[Mayer-Rokitansky-Hauser syndrome|Mayer-Rokitansky-Kuster-Hauser syndrome]]
*[[Turner's syndrome]]<ref name="pmid10344582">{{cite journal| author=Hovatta O| title=Pregnancies in women with Turner's syndrome. | journal=Ann Med | year= 1999 | volume= 31 | issue= 2 | pages= 106-10 | pmid=10344582 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10344582  }} </ref>
* [[Kallmann syndrome]]
*[[Mayer-Rokitansky-Hauser syndrome|Mayer-Rokitansky-Kuster-Hauser syndrome]]
* [[Primary ciliary dyskinesia]]
*[[Kallmann syndrome]]
*[[Primary ciliary dyskinesia]]


===Endocrine causes===
===Endocrine causes===
* [[Hypothyroidism]]
 
* [[Hypopituitarism]]
*[[Hypothyroidism]]<ref name="pmid24139473">{{cite journal| author=Luciano AA, Lanzone A, Goverde AJ| title=Management of female infertility from hormonal causes. | journal=Int J Gynaecol Obstet | year= 2013 | volume= 123 Suppl 2 | issue=  | pages= S9-17 | pmid=24139473 | doi=10.1016/j.ijgo.2013.09.007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24139473  }} </ref>
* [[Hyperprolactinemia]]
*[[Hypopituitarism]]
* [[Polycystic ovarian syndrome]]
*[[Hyperprolactinemia]]
* [[Congenital adrenal hyperplasia]]
*[[Polycystic ovarian syndrome]]
* Hypogonadotropic hypergonadism
*[[Congenital adrenal hyperplasia]]
*Hypogonadotropic hypergonadism
 
===Ovarian causes===
===Ovarian causes===
* [[Anovulation]]
 
* [[Luteal phase]] defect
*[[Anovulation]]
* Luteinised unruptured follicle
*[[Luteal phase]] defect
*Luteinised unruptured follicle


===Tubal causes===
===Tubal causes===
* [[Pelvic inflammatory disease]] causing adhesions and endosalpingeal damage
 
* Previous tubal surgery  
*[[Pelvic inflammatory disease]] causing adhesions and endosalpingeal damage
* Tubal [[endometriosis]]
*Previous tubal [[surgery]]
*Tubal [[endometriosis]]
 
===Uterine causes===
===Uterine causes===
* [[Polyps]]<ref name="pmid24119894">{{cite journal| author=Abrao MS, Muzii L, Marana R| title=Anatomical causes of female infertility and their management. | journal=Int J Gynaecol Obstet | year= 2013 | volume= 123 Suppl 2 | issue=  | pages= S18-24 | pmid=24119894 | doi=10.1016/j.ijgo.2013.09.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24119894  }} </ref>
 
* [[Fibroids]]
*[[Polyps]]<ref name="pmid24119894">{{cite journal| author=Abrao MS, Muzii L, Marana R| title=Anatomical causes of female infertility and their management. | journal=Int J Gynaecol Obstet | year= 2013 | volume= 123 Suppl 2 | issue=  | pages= S18-24 | pmid=24119894 | doi=10.1016/j.ijgo.2013.09.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24119894  }} </ref>
* [[Endometriosis]]<ref name="pmid354978">{{cite journal| author=Czernobilsky B| title=Endometritis and infertility. | journal=Fertil Steril | year= 1978 | volume= 30 | issue= 2 | pages= 119-30 | pmid=354978 | doi=10.1016/s0015-0282(16)43448-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=354978 }} </ref>
*[[Fibroids]]
* Congenital uterine anomalies such as septate uterus  
*[[Endometriosis]]<ref name="pmid27998009">{{cite journal| author=Tanbo T, Fedorcsak P| title=Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. | journal=Acta Obstet Gynecol Scand | year= 2017 | volume= 96 | issue= 6 | pages= 659-667 | pmid=27998009 | doi=10.1111/aogs.13082 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27998009 }} </ref>
* Uterine hypoplasia
*[[Congenital]] [[uterine]] anomalies such as septate uterus
*[[Uterine]] [[hypoplasia]]


===Cervical factors===
===Cervical factors===
* Congenital elongation of cervix
 
* [[Uterine prolapse]]
*Congenital elongation of [[cervix]]
* Cauterization of cervix
*[[Uterine prolapse]]
*Cauterization of [[cervix]]
 
===Vaginal factors===
===Vaginal factors===
* Vaginal atresia
 
* Transverse [[vaginal septum]]
*[[Vaginal]] atresia
* Septate vagina
*Transverse [[vaginal septum]]
* [[Vaginitis]]
*Septate [[vagina]]
*[[Vaginitis]]
 
===Miscellaneous factors===
===Miscellaneous factors===
* Advanced age
 
* [[Anxiety]]
*Advanced age
* [[Dyspareunia]]
*[[Anxiety]]
* [[Contraceptive]] use
*[[Dyspareunia]]
*[[Contraceptive]] use


==Diagnosis==
==Diagnosis==
Shown below is an algorithm summarizing the diagnosis of female infertility <ref name="pmid14519712">{{cite journal| author=Smith S, Pfeifer SM, Collins JA| title=Diagnosis and management of female infertility. | journal=JAMA | year= 2003 | volume= 290 | issue= 13 | pages= 1767-70 | pmid=14519712 | doi=10.1001/jama.290.13.1767 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14519712  }} </ref>.
Shown below is an algorithm summarizing the [[diagnosis]] of female infertility according to the American College of Gynecology and Obstetricians 2019 Committee Opinion on Infertility Workup for the Woman's Health Specialist and Evaluation, Global Infertility Guidelines published in 1992 by the [[WHO]], updated in 2012, and The Treatment of Infertility Guidelines by the American Family Physician. <ref name="pmid14519712">{{cite journal| author=Smith S, Pfeifer SM, Collins JA| title=Diagnosis and management of female infertility. | journal=JAMA | year= 2003 | volume= 290 | issue= 13 | pages= 1767-70 | pmid=14519712 | doi=10.1001/jama.290.13.1767 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14519712  }} </ref><ref name="pmid31135764">{{cite journal| author=| title=Infertility Workup for the Women's Health Specialist: ACOG Committee Opinion, Number 781. | journal=Obstet Gynecol | year= 2019 | volume= 133 | issue= 6 | pages= e377-e384 | pmid=31135764 | doi=10.1097/AOG.0000000000003271 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31135764  }} </ref><ref name="pmid25822387">{{cite journal| author=Lindsay TJ, Vitrikas KR| title=Evaluation and treatment of infertility. | journal=Am Fam Physician | year= 2015 | volume= 91 | issue= 5 | pages= 308-14 | pmid=25822387 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25822387  }} </ref><ref name="pmid1642014">{{cite journal| author=| title=Recent advances in medically assisted conception. Report of a WHO Scientific Group. | journal=World Health Organ Tech Rep Ser | year= 1992 | volume= 820 | issue=  | pages= 1-111 | pmid=1642014 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1642014  }} </ref>
 
'''Abbreviations''': '''STD''' - [[Sexually transmitted disease]], '''FSH''' - [[Follicle stimulating hormone]], '''LH''' - [[Luteinizing hormone]], '''TSH''' - [[Thyroid stimulating hormone]], '''CT''' - [[Computed tomography]], '''MRI''' - [[Magnetic resonance imaging]], '''IVF''' - [[In vitro fertilization]]
 
{{familytree/start |summary=PE diagnosis infertility.}}
{{familytree/start |summary=PE diagnosis infertility.}}
{{familytree | | | | | | | | A01 | | | A01=Couple with infertility }}
{{familytree | | | | | | | | A01 | | | A01=Couple with infertility }}
{{familytree | | | | | | | | |!| | | | }}
{{familytree | | | | | | | | |!| | | | }}
{{familytree | | | | | | | | B01 |B01=<div style="float: left; text-align: left; line-height: 150% ">'''Detailed history''' including <br>❑ Any history of abdominal or pelvic [[surgery]]? <br>❑ [[Menstruation|Menstrual history]] <br>❑ History of [[contraceptive]] use <br>❑ Obstetric history</div>}}
{{familytree | | | | | | | | B01 |B01=<div style="float: left; text-align: left; line-height: 150% ">'''Detailed history''' including <br>❑ Any history of [[abdominal]] or [[pelvic]] [[surgery]]? <br>❑ [[Menstruation|Menstrual history]] <br>❑ History of [[contraceptive]] use <br>❑ Obstetric history <br>❑ Any history of [[diethylstilbestrol]] exposure <br>❑ Frequency of intercourse <br>❑ Any history of [[Sexually transmitted disease|STDs]] in either partner <br>❑ History of [[acne]], [[hirsutism]] or recent weight changes </div>}}
{{familytree | | | | | | | | |!|}}
{{familytree | | | | | | | | |!|}}
{{familytree | | | | | | | | C01 | | | C01= '''Initial investigations'''}}
{{familytree | | | | | | | | C01 | | | C01=<div style="float: left; text-align: left; line-height: 150% ">'''Physical examination''' <br>❑ [[Height]], [[weight]] and [[Body mass index|BMI]] <br> '''Head and neck examination''' for <br>❑ [[Exophthalmos]] <br>❑ Webbed neck <br>❑ [[Epicanthal fold]] <br>❑ Presence of any [[neck]] [[swelling]]s <br>❑ [[Breast examination]] for any swellings or [[nipple]] discharge <br>❑ Any swellings in the [[abdomen]] <br> Thorough '''gynecological exam''' including <br>❑ Distribution of [[pubic hair]] <br>❑ If there is presence of any [[clitoris|clitoral]] enlargement <br>❑ Signs of [[Sexually transmitted disease|STDs]] <br> '''Bimanual exam''' might detect the presence of <br>❑ [[Uterine fibroids]] <br>❑ [[Cervical motion tenderness]] <br>❑ Presence of vaginal septae}}
{{familytree | | | | | | | | |!| | | |}}
{{familytree | | | | | | | | |!| | | |}}
{{familytree | | | | | | | | D01 | | | | | | | |D01=<div style="float: left; text-align: left; line-height: 150% ">❑ [[Urine]] examination <br>❑ [[Complete blood count]] <br>❑ Fasting and post prandial blood sugar estimation <br>❑ [[Semen]] analysis </div>}}
{{familytree | | | | | | | | D01 | | | | | | | |D01=<div style="float: left; text-align: left; line-height: 150% ">'''Initial investigations'''<br>❑ [[Urine]] examination <br>❑ [[Complete blood count]] <br>❑ Fasting and post prandial blood sugar estimation <br>❑ [[Semen]] analysis <br>❑ [[Hysterosalpingography]]</div>}}
{{familytree | | | | | | | | |!| | | | | | | | | |}}
{{familytree | | | | | | | | |!| | | | | | | | | |}}
{{familytree | | | | | | | | E01 |E01=Normal semen analysis}}
{{familytree | | | | | | | | E01 |E01=Normal semen analysis}}
Line 69: Line 103:
{{familytree | F01 | | | | | F02 | | | F03 | | | F04 |F01=[[Ovary|Ovarian causes]]|F02=[[Endometrium|Endometrial causes]]|F03=[[Cervix|Cervical causes]]|F04=[[Fallopian tube]] causes}}
{{familytree | F01 | | | | | F02 | | | F03 | | | F04 |F01=[[Ovary|Ovarian causes]]|F02=[[Endometrium|Endometrial causes]]|F03=[[Cervix|Cervical causes]]|F04=[[Fallopian tube]] causes}}
{{familytree | |!| | | | | | |!| | | | |!| | | | |!|}}
{{familytree | |!| | | | | | |!| | | | |!| | | | |!|}}
{{familytree | G01 | | | | | G02 | | | G03 | | | G04 |G01=<div style="float: left; text-align: left; line-height: 150% ">'''Methods to detect ovulation''' <br>❑ Basal body temperature measurement throughout cycle <br>❑ Vaginal cytology <br>❑ Cervical mucus study <br>❑ Serum [[progesterone]] <br>❑ Serum [[Lutenizing hormone]] <br>❑ Serum [[estradiol]] <br>❑ Urine [[Lutenizing hormone]] level <br>❑ [[Transvaginal ultrasound]]|G02=Endometrial [[biopsy]] on day 21-23|G03= Cervical mucus study/ Sperm cervical mucus contact test|G04=<div style="float: left; text-align: left; line-height: 150% ">❑ [[Hysterosalpingography]] <br>❑ [[Laproscopy]]</div>}}
{{familytree | G01 | | | | | G02 | | | G03 | | | G04 |G01=<div style="float: left; text-align: left; line-height: 150% ">'''Methods to detect ovulation''' <br>❑ Basal body temperature measurement throughout cycle <br>❑ Vaginal cytology <br>❑ Cervical mucus study <br>❑ Serum [[progesterone]] <br>❑ Serum [[Luteinizing hormone]] <br>❑ Serum [[estradiol]] <br>❑ Urine [[Luteinizing hormone]] level <br>❑ [[Transvaginal ultrasound]]|G02=Endometrial [[biopsy]] on day 21-23|G03= Cervical mucus study/ Sperm cervical mucus contact test|G04=<div style="float: left; text-align: left; line-height: 150% ">❑ [[Hysterosalpingography]] <br>❑ [[Laparoscopy]]</div>}}
{{familytree | |!| | | | | | |!| | | | |!| | | | |}}
{{familytree | |!| | | | | | |!| | | | |!| | | | |}}
{{familytree |,|^|-|-|.| | | |!| |,|-|-|^|-|-|.|}}
{{familytree |,|^|-|-|.| | | |!| |,|-|-|^|-|-|.|}}
{{familytree | H01 | | H02 | |!| | H03 | | | H04|H01=Anovulatory cycle|H02=Ovulatory cycle|H03=Progressive motile sperm seen|H04=Sperm antibodies}}
{{familytree | H01 | | H02 | |!| | H03 | | | H04|H01=Anovulatory cycle|H02=Ovulatory cycle|H03=Progressive motile sperm seen|H04=Sperm antibodies}}
{{familytree | |!| | | |!| | |!| | | | | | | |!|}}
{{familytree | |!| | | |!| | |!| | | | | | | |!|}}
{{familytree | I01 | | I02 | |!| | | | | | | I03|I01=<div style="float: left; text-align: left; line-height: 150% ">'''Investigate the following''' <br>❑ Serum [[Follicle stimulating hormone|FSH]] <br>❑ Serum [[Lutenizing hormone|LH]] <br>❑ Serum [[Prolactin]] <br>❑ [[Thyroid stimulating hormone|TSH]] level <br>❑ If [[hirsutism]] is present check [[testosterone]] levels and [[17-Hydroxyprogesterone]] levels <br>❑ If [[Follicle stimulating hormone|FSH]] and [[Lutenizing hormone|LH]] levels are in the low-normal range, but with high [[prolactin]], consider [[CT]] or [[MRI]] of the [[head]]|I02=If age is >30 years, work up with all other investigations including day 3 [[Follicle stimulating hormone|FSH]]|I03= Occasionally, IgG, IgA or IgM antibodies are found against sperm. Treating these anti-sperm antibodies have not shown an improved outcome in pregnancies. Treatment is along the lines of [[IVF]] </div>}}
{{familytree | I01 | | I02 | |!| | | | | | | I03|I01=<div style="float: left; text-align: left; line-height: 150% ">'''Investigate the following''' <br>❑ Serum [[Follicle stimulating hormone|FSH]] <br>❑ Serum [[Luteinizing hormone|LH]] <br>❑ Serum [[Prolactin]] <br>❑ [[Thyroid stimulating hormone|TSH]] level <br>❑ If [[hirsutism]] is present check [[testosterone]] levels and [[17-Hydroxyprogesterone]] levels <br>❑ If [[Follicle stimulating hormone|FSH]] and [[Luteinizing hormone|LH]] levels are in the low-normal range, but with high [[prolactin]], consider [[CT]] or [[MRI]] of the [[head]]|I02=If age is >30 years, work up with all other investigations including day 3 [[Follicle stimulating hormone|FSH]]|I03= Occasionally, IgG, IgA or IgM antibodies are found against sperm. Treating these anti-sperm antibodies have not shown an improved outcome in pregnancies. Treatment is along the lines of [[IVF]] </div>}}
{{familytree | |!| | |,|-|-|-|^|-|-|-|.|}}
{{familytree | |!| | |,|-|-|-|^|-|-|-|.|}}
{{familytree | |!| | |!| | | | | | | |!|}}
{{familytree | |!| | |!| | | | | | | |!|}}
{{familytree | |`|-| J01 | | | | | | J02 |J01=Non secretory endometrium|J02=Secretory endometrium}}
{{familytree | |`|-| J01 | | | | | | J02 |J01=Non secretory [[endometrium]]|J02=Secretory [[endometrium]]}}
{{familytree | | | | | | | | | | | | |!|}}
{{familytree | | | | | | | | | | | | |!|}}
{{familytree | | | | | | | | | | | | K01 |K01=Luteal phase defect}}
{{familytree | | | | | | | | | | | | K01 |K01=[[Luteal phase]] defect}}
{{familytree | | | | | | | | | | | | |!|}}
{{familytree | | | | | | | | | | | | |!|}}
{{familytree | | | | | | | | | | | | L01 |L01=Confirmed by basal body temperature or repeat endometrial biopsy and serum progesterone estimated on 8th day}}
{{familytree | | | | | | | | | | | | L01 |L01=Confirmed by [[basal body temperature]] or repeat [[endometrium|endometrial]] [[biopsy]] and serum [[progesterone]] estimated on 8th day}}
{{familytree/end}}
{{familytree/end}}


==Treatment==
==Treatment==
Shown below is an algorithm summarizing the treatment of infertility.
Shown below is an algorithm summarizing the treatment of infertility. <ref name="pmid23182559">{{cite journal| author=Macer ML, Taylor HS| title=Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. | journal=Obstet Gynecol Clin North Am | year= 2012 | volume= 39 | issue= 4 | pages= 535-49 | pmid=23182559 | doi=10.1016/j.ogc.2012.10.002 | pmc=3538128 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23182559  }} </ref><ref name="pmid27998009">{{cite journal| author=Tanbo T, Fedorcsak P| title=Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. | journal=Acta Obstet Gynecol Scand | year= 2017 | volume= 96 | issue= 6 | pages= 659-667 | pmid=27998009 | doi=10.1111/aogs.13082 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27998009  }} </ref>
 
'''Abbreviations''': '''hMG'''- [[Menotropins|Human menopausal gonadotropin]], '''FSH'''- [[Follicle stimulating hormone]], '''CAH'''- [[Congenital adrenal hyperplasia]], '''ART'''- [[Assisted reproductive technology]], '''PCOS'''- [[Polycystic ovarian syndrome]]
{{familytree/start |summary=Infertility treatment Algorithm.}}
{{familytree/start |summary=Infertility treatment Algorithm.}}
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | | A01 |A01= Thorough history and initial investigations}}  
{{familytree | | | | | | | | | | | | | | | | | | | | | | | | | | A01 |A01= Thorough history and initial investigations}}  
{{familytree | | | |,|-|-|-|-|-|v|-|-|-|-|-|-|-|v|-|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|v|-|-|-|-|-|-|-|.|}}
{{familytree | | | |,|-|-|-|-|-|v|-|-|-|-|-|-|-|v|-|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|v|-|-|-|-|.|}}
{{familytree | | | B01 | | | | B02 | | | | | | B03 | | | | | | | B04 | | | | | | B05 | | | | | | B06|B01=Ovulatory causes|B02=Tubal causes|B03=Cervical causes|B04=Endocrinopathies|B05=Uterine causes|B06=Other causes}}
{{familytree | | | B01 | | | | B02 | | | | | | B03 | | | | | | | B04 | | | | | | B05 | | | B06|B01=Ovulatory [[causes]]|B02=Tubal [[causes]]|B03=Cervical [[causes]]|B04=Endocrinopathies|B05=[[Uterine]] [[causes]]|B06=Other [[causes]]}}
{{familytree |,|-|-|^|-|.| | | |!| | | | | | | |!| | | | | | | | |!| | | | | | | |!| | | | | | | |!|}}
{{familytree |,|-|-|^|-|.| | | |!| | | | | | | |!| | | | | | | | |!| | | | | | | |!| | | | |!|}}
{{familytree | C01 | | C02 | | |!| | | | | | | C03 | | | | | | | |!| | | | | | | C04 | | | | | | |!|C01=<div style="float: left; text-align: left; line-height: 150% ">'''Anovulation''' <br> Induction of ovulation can be done by <br>❑ [[Clomiphene citrate]] <br>❑ hMG <br>❑ Purified/recombinant [[Follicle Stimulating Hormone|FSH]] <br>❑ [[Gonadotropin-releasing hormone]] and its analogues|C02=<div style="float: left; text-align: left; line-height: 150% ">'''Correction of biochemical abnormalities''' <br>❑ [[Hyperinsulinemia]] or [[insulin]] resistance - [[Metformin]] <br>❑ [[Hyperprolactinemia]] - [[Bromocriptine]]|C03=<div style="float: left; text-align: left; line-height: 150% ">❑ [[Cervicitis]] is treated with [[doxycycline]] or other [[antibiotic]]s  <br>❑ Quality of cervical mucus is improved with oral [[estrogen]]|C04=<div style="float: left; text-align: left; line-height: 150% ">❑[[Uterine fibroids]] are treated by [[myomectomy]] <br>❑ [[Septate uterus|Uterine septum]] is corrected by a metroplasty <br>❑ [[Polyp]]s are treated by polypectomy <br>❑ Hysteroscopic adhesiolysis in cases of synechiae </div>}}
{{familytree | C01 | | C02 | | |!| | | | | | | C03 | | | | | | | |!| | | | | | | C04 | | | |!|C01=<div style="float: left; text-align: left; line-height: 150% ">'''[[Anovulation]]''' <br> Induction of [[ovulation]] can be done by <br>❑ [[Clomiphene citrate]] <br>❑ [[hMG]] <br>❑ Purified/recombinant [[Follicle Stimulating Hormone|FSH]] <br>❑ [[Gonadotropin-releasing hormone]] and its analogues <br> '''[[Assisted reproductive techniques]]''' such as <br>❑ [[In vitro fertilization]] <br>❑ cryopreservation of [[gamete]]s or fertilized [[embryo]]s <br>❑ [[Intracytoplasmic sperm injection]] <br>❑ Egg donation via donors|C02=<div style="float: left; text-align: left; line-height: 150% ">'''Correction of biochemical abnormalities''' <br>❑ [[Hyperinsulinemia]] or [[insulin]] resistance - [[Metformin]] <br>❑ [[Hyperprolactinemia]] - [[Bromocriptine]]|C03=<div style="float: left; text-align: left; line-height: 150% ">❑ [[Cervicitis]] is treated with [[doxycycline]] or other [[antibiotic]]s  <br>❑ Quality of cervical mucus is improved with oral [[estrogen]]|C04=<div style="float: left; text-align: left; line-height: 150% ">❑[[Uterine fibroids]] are treated by [[myomectomy]] <br>❑ [[Septate uterus|Uterine septum]] is corrected by a metroplasty <br>❑ [[Polyp]]s are treated by polypectomy <br>❑ Hysteroscopic adhesiolysis in cases of synechiae </div>}}
{{familytree | | | | | | | | | |!| | | | | | | | | | | | | | | | D01 | | | | | | | | | | | |!|D01=<div style="float: left; text-align: left; line-height: 150% ">❑ Uncontrolled [[diabetes]] must be treated before exploring other options <br>❑ [[Hyperthyroidism]] and [[Grave's disease]] causing infertility can be corrected with antithyroid drugs <br>❑ [[Hypothyroidism]] induced infertility is corrected when euthyroid state is achieved <br>❑ [[Congenital Adrenal Hyperplasia|CAH]] causes infertility which can be corrected with [[clomiphene]] and other [[ovulation]] induction techniques <br> [[Assisted reproductive technology|ARTs]] are used when [[ovulation]] stimulation fails <br>❑ Treating infertility in [[PCOS]] is a multidisciplinary approach and involves <br> Glycemic control with [[metformin]] <br> Reduction of weight when applicable <br> [[Oral contraceptive pill]]s <br> [[Ovulation]] induction with [[clomiphene]] <br> Antiandrogens such as [[flutamide]] and [[spironolactone]] for [[acne]] and [[hirsutism]] <br>❑ [[Hyperprolactinemia]] induced infertility is treated with [[dopamine agonist]]s such as [[cabergoline]]</div>}}
{{familytree | | | | | | | | | E01 | | | | | | | | | | | | | | | | | | | | | | | | | | | | E02 |E01=<div style="float: left; text-align: left; line-height: 150% ">❑'''[[Pelvic inflammatory disease]]''' - Identify the infecting agent and start appropriate [[antibiotic]] therapy <br> Treat sexual partner for any [[Sexually transmitted infection|STIs]] <br>❑ '''Adhesions'''- [[surgical]] correction <br>❑ [[In vitro fertilization]]|E02=<div style="float: left; text-align: left; line-height: 150% ">'''Unexplained infertility''' is a [[diagnosis]] of exclusion after semen analysis and all other tests are normal <br> Treatment can include the following <br>❑ [[Ovulation]] induction with [[clomiphene]] <br>❑ [[Intrauterine insemination]] <br>❑ [[Invitro fertilization]]</div>}}
{{familytree/end}}
{{familytree/end}}


==Do's==
==Dos==
* The content in this section is in bullet points.
 
*Prompt and early treatment of [[PID]] must be done to prevent infertility. <ref name="pmid16597205">{{cite journal| author=Haggerty CL, Ness RB| title=Epidemiology, pathogenesis and treatment of pelvic inflammatory disease. | journal=Expert Rev Anti Infect Ther | year= 2006 | volume= 4 | issue= 2 | pages= 235-47 | pmid=16597205 | doi=10.1586/14787210.4.2.235 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16597205  }} </ref>
*Effective counseling about male and female components of infertility.
*Educate the [[patient]] about toxic effects of [[nicotine]], [[marijuana]], and other drugs and their impact on fertility if the patient is a known user. <ref name="pmid28754351">{{cite journal| author=Messi E, Pimpinelli F, Andrè V, Rigobello C, Gotti C, Maggi R| title=The alpha-7 nicotinic acetylcholine receptor is involved in a direct inhibitory effect of nicotine on GnRH release: In vitro studies. | journal=Mol Cell Endocrinol | year= 2018 | volume= 460 | issue=  | pages= 209-218 | pmid=28754351 | doi=10.1016/j.mce.2017.07.025 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28754351  }} </ref>
*Risk of [[ectopic pregnancy]], [[multiple gestation]]s and [[ovarian hyperstimulation syndrome]] must be explained.<ref name="pmid29883983">{{cite journal| author=Shah JS, Roman T, Viteri OA, Haidar ZA, Ontiveros A, Sibai BM| title=The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations. | journal=Am J Perinatol | year= 2018 | volume= 35 | issue= 14 | pages= 1388-1393 | pmid=29883983 | doi=10.1055/s-0038-1660457 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29883983  }} </ref>


==Don'ts==
==Don'ts==
* The content in this section is in bullet points.
 
*Don't ignore the risk of [[ovarian hyperstimulation syndrome]] in [[patients]] undergoing [[ovulation]] induction, particularly in [[patients]] who have had [[PCOS]]. <ref name="pmid28262238">{{cite journal| author=Nelson SM| title=Prevention and management of ovarian hyperstimulation syndrome. | journal=Thromb Res | year= 2017 | volume= 151 Suppl 1 | issue=  | pages= S61-S64 | pmid=28262238 | doi=10.1016/S0049-3848(17)30070-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28262238  }} </ref>
*Don't pursue [[assisted reproductive technology]] without first correcting underlying [[endocrinopathy]] when present.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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Latest revision as of 15:03, 8 February 2021


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sanjana Nethagani, M.B.B.S.[2]

Synonyms and keywords: Approach to Infertility, Approach to subfertility, Approach to impotence

Infertility Resident Survival Guide Microchapters
Overview
Causes
Diagnosis
Treatment
Dos
Don'ts


Overview

Infertility is defined as a failure to conceive after one or more years of unprotected intercourse. Infertility is divided broadly into primary and secondary infertility where primary infertility is failure to conceive and secondary infertility is failure to conceive after a previous pregnancy. Multiple factors play a role in conception and infertility such as healthy spermatozoa, regular ovulation, patent fallopian tubes, normal uterine cavity etc.

Causes

Common causes of female infertility are listed below.

Genetic causes

Endocrine causes

Ovarian causes

Tubal causes

Uterine causes

Cervical factors

Vaginal factors

Miscellaneous factors

Diagnosis

Shown below is an algorithm summarizing the diagnosis of female infertility according to the American College of Gynecology and Obstetricians 2019 Committee Opinion on Infertility Workup for the Woman's Health Specialist and Evaluation, Global Infertility Guidelines published in 1992 by the WHO, updated in 2012, and The Treatment of Infertility Guidelines by the American Family Physician. [5][6][7][8]

Abbreviations: STD - Sexually transmitted disease, FSH - Follicle stimulating hormone, LH - Luteinizing hormone, TSH - Thyroid stimulating hormone, CT - Computed tomography, MRI - Magnetic resonance imaging, IVF - In vitro fertilization

 
 
 
 
 
 
 
Couple with infertility
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Detailed history including
❑ Any history of abdominal or pelvic surgery?
Menstrual history
❑ History of contraceptive use
❑ Obstetric history
❑ Any history of diethylstilbestrol exposure
❑ Frequency of intercourse
❑ Any history of STDs in either partner
❑ History of acne, hirsutism or recent weight changes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination
Height, weight and BMI
Head and neck examination for
Exophthalmos
❑ Webbed neck
Epicanthal fold
❑ Presence of any neck swellings
Breast examination for any swellings or nipple discharge
❑ Any swellings in the abdomen
Thorough gynecological exam including
❑ Distribution of pubic hair
❑ If there is presence of any clitoral enlargement
❑ Signs of STDs
Bimanual exam might detect the presence of
Uterine fibroids
Cervical motion tenderness
❑ Presence of vaginal septae
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initial investigations
Urine examination
Complete blood count
❑ Fasting and post prandial blood sugar estimation
Semen analysis
Hysterosalpingography
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normal semen analysis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ovarian causes
 
 
 
 
Endometrial causes
 
 
Cervical causes
 
 
Fallopian tube causes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Methods to detect ovulation
❑ Basal body temperature measurement throughout cycle
❑ Vaginal cytology
❑ Cervical mucus study
❑ Serum progesterone
❑ Serum Luteinizing hormone
❑ Serum estradiol
❑ Urine Luteinizing hormone level
Transvaginal ultrasound
 
 
 
 
Endometrial biopsy on day 21-23
 
 
Cervical mucus study/ Sperm cervical mucus contact test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anovulatory cycle
 
Ovulatory cycle
 
 
 
 
Progressive motile sperm seen
 
 
Sperm antibodies
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigate the following
❑ Serum FSH
❑ Serum LH
❑ Serum Prolactin
TSH level
❑ If hirsutism is present check testosterone levels and 17-Hydroxyprogesterone levels
❑ If FSH and LH levels are in the low-normal range, but with high prolactin, consider CT or MRI of the head
 
If age is >30 years, work up with all other investigations including day 3 FSH
 
 
 
 
 
 
 
 
 
Occasionally, IgG, IgA or IgM antibodies are found against sperm. Treating these anti-sperm antibodies have not shown an improved outcome in pregnancies. Treatment is along the lines of IVF
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Non secretory endometrium
 
 
 
 
 
Secretory endometrium
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Luteal phase defect
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirmed by basal body temperature or repeat endometrial biopsy and serum progesterone estimated on 8th day

Treatment

Shown below is an algorithm summarizing the treatment of infertility. [9][4]

Abbreviations: hMG- Human menopausal gonadotropin, FSH- Follicle stimulating hormone, CAH- Congenital adrenal hyperplasia, ART- Assisted reproductive technology, PCOS- Polycystic ovarian syndrome

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thorough history and initial investigations
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ovulatory causes
 
 
 
Tubal causes
 
 
 
 
 
Cervical causes
 
 
 
 
 
 
Endocrinopathies
 
 
 
 
 
Uterine causes
 
 
Other causes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Anovulation
Induction of ovulation can be done by
Clomiphene citrate
hMG
❑ Purified/recombinant FSH
Gonadotropin-releasing hormone and its analogues
Assisted reproductive techniques such as
In vitro fertilization
❑ cryopreservation of gametes or fertilized embryos
Intracytoplasmic sperm injection
❑ Egg donation via donors
 
Correction of biochemical abnormalities
Hyperinsulinemia or insulin resistance - Metformin
Hyperprolactinemia - Bromocriptine
 
 
 
 
 
 
 
 
 
 
Cervicitis is treated with doxycycline or other antibiotics
❑ Quality of cervical mucus is improved with oral estrogen
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Uterine fibroids are treated by myomectomy
Uterine septum is corrected by a metroplasty
Polyps are treated by polypectomy
❑ Hysteroscopic adhesiolysis in cases of synechiae
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
❑ Uncontrolled diabetes must be treated before exploring other options
Hyperthyroidism and Grave's disease causing infertility can be corrected with antithyroid drugs
Hypothyroidism induced infertility is corrected when euthyroid state is achieved
CAH causes infertility which can be corrected with clomiphene and other ovulation induction techniques
ARTs are used when ovulation stimulation fails
❑ Treating infertility in PCOS is a multidisciplinary approach and involves
Glycemic control with metformin
Reduction of weight when applicable
Oral contraceptive pills
Ovulation induction with clomiphene
Antiandrogens such as flutamide and spironolactone for acne and hirsutism
Hyperprolactinemia induced infertility is treated with dopamine agonists such as cabergoline
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pelvic inflammatory disease - Identify the infecting agent and start appropriate antibiotic therapy
Treat sexual partner for any STIs
Adhesions- surgical correction
In vitro fertilization
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unexplained infertility is a diagnosis of exclusion after semen analysis and all other tests are normal
Treatment can include the following
Ovulation induction with clomiphene
Intrauterine insemination
Invitro fertilization

Dos

Don'ts

References

  1. Hovatta O (1999). "Pregnancies in women with Turner's syndrome". Ann Med. 31 (2): 106–10. PMID 10344582.
  2. Luciano AA, Lanzone A, Goverde AJ (2013). "Management of female infertility from hormonal causes". Int J Gynaecol Obstet. 123 Suppl 2: S9–17. doi:10.1016/j.ijgo.2013.09.007. PMID 24139473.
  3. Abrao MS, Muzii L, Marana R (2013). "Anatomical causes of female infertility and their management". Int J Gynaecol Obstet. 123 Suppl 2: S18–24. doi:10.1016/j.ijgo.2013.09.008. PMID 24119894.
  4. 4.0 4.1 Tanbo T, Fedorcsak P (2017). "Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options". Acta Obstet Gynecol Scand. 96 (6): 659–667. doi:10.1111/aogs.13082. PMID 27998009.
  5. Smith S, Pfeifer SM, Collins JA (2003). "Diagnosis and management of female infertility". JAMA. 290 (13): 1767–70. doi:10.1001/jama.290.13.1767. PMID 14519712.
  6. "Infertility Workup for the Women's Health Specialist: ACOG Committee Opinion, Number 781". Obstet Gynecol. 133 (6): e377–e384. 2019. doi:10.1097/AOG.0000000000003271. PMID 31135764.
  7. Lindsay TJ, Vitrikas KR (2015). "Evaluation and treatment of infertility". Am Fam Physician. 91 (5): 308–14. PMID 25822387.
  8. "Recent advances in medically assisted conception. Report of a WHO Scientific Group". World Health Organ Tech Rep Ser. 820: 1–111. 1992. PMID 1642014.
  9. Macer ML, Taylor HS (2012). "Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility". Obstet Gynecol Clin North Am. 39 (4): 535–49. doi:10.1016/j.ogc.2012.10.002. PMC 3538128. PMID 23182559.
  10. Haggerty CL, Ness RB (2006). "Epidemiology, pathogenesis and treatment of pelvic inflammatory disease". Expert Rev Anti Infect Ther. 4 (2): 235–47. doi:10.1586/14787210.4.2.235. PMID 16597205.
  11. Messi E, Pimpinelli F, Andrè V, Rigobello C, Gotti C, Maggi R (2018). "The alpha-7 nicotinic acetylcholine receptor is involved in a direct inhibitory effect of nicotine on GnRH release: In vitro studies". Mol Cell Endocrinol. 460: 209–218. doi:10.1016/j.mce.2017.07.025. PMID 28754351.
  12. Shah JS, Roman T, Viteri OA, Haidar ZA, Ontiveros A, Sibai BM (2018). "The Relationship of Assisted Reproductive Technology on Perinatal Outcomes in Triplet Gestations". Am J Perinatol. 35 (14): 1388–1393. doi:10.1055/s-0038-1660457. PMID 29883983.
  13. Nelson SM (2017). "Prevention and management of ovarian hyperstimulation syndrome". Thromb Res. 151 Suppl 1: S61–S64. doi:10.1016/S0049-3848(17)30070-1. PMID 28262238.