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Primary tubal infertility

Last edited: 2 h ago

Overview

Primary tubal infertility arises from damage to the fallopian tubes, impairing their ability to facilitate fertilization and transport the embryo to the uterus. This condition constitutes a significant proportion of female infertility cases, accounting for 25–35% of all infertility issues 1. It often results from pelvic inflammatory disease, previous gynecological surgeries, endometriosis, and other inflammatory processes that lead to tubal obstruction, fibrosis, and impaired function. The clinical significance lies in its substantial impact on reproductive health, affecting women's ability to conceive naturally. Given its prevalence and the increasing incidence, particularly among women over 35 years old, accurate diagnosis and effective management are crucial in day-to-day clinical practice to restore fertility or guide alternative reproductive strategies.

Pathophysiology

Primary tubal infertility develops through a cascade of events initiated by inflammatory insults such as pelvic inflammatory disease (PID) or surgical interventions. Chronic inflammation triggers a cascade of cellular responses, including the activation of immune cells and the release of pro-inflammatory cytokines, leading to tissue damage and fibrosis 1. This inflammatory environment promotes the formation of adhesions and strictures within the fallopian tubes, compromising their patency and function. Molecularly, alterations in ciliary beating frequency and epithelial integrity further impede the transport of gametes and embryos, contributing to the obstruction and reduced fertility 4. Additionally, factors like endometriosis and previous abdominal surgeries exacerbate these changes, often resulting in irreversible structural damage that hinders natural conception.

Epidemiology

The incidence of tubal infertility varies globally but consistently affects approximately 25–35% of infertile women 1. It disproportionately impacts women over 35 years old, where it emerges as a leading cause of infertility 1. Risk factors include a history of pelvic inflammatory disease, ectopic pregnancies, previous pelvic surgeries, and conditions like endometriosis 23. Geographic variations exist, with higher prevalence noted in regions with limited access to healthcare and higher rates of sexually transmitted infections, which can predispose individuals to PID 1. Over time, trends suggest an increasing incidence linked to delayed childbearing and improved diagnostic capabilities, highlighting the ongoing relevance of this condition in reproductive medicine.

Clinical Presentation

Women with primary tubal infertility often present with primary or secondary infertility, characterized by the inability to conceive despite regular unprotected intercourse for at least one year (primary) or following a previous pregnancy (secondary). Typical presentations may lack specific symptoms unless complicated by ectopic pregnancy or recurrent pelvic pain. Red-flag features include irregular menstrual cycles, pelvic pain, and a history suggestive of risk factors such as PID or previous surgeries 1. Diagnosis often requires a thorough reproductive history and exclusion of other infertility causes through clinical evaluation and diagnostic testing.

Diagnosis

The diagnostic approach for primary tubal infertility typically begins with a comprehensive reproductive history and physical examination, followed by specific diagnostic tests to confirm tubal pathology. Key diagnostic criteria and tests include:

  • Hysterosalpingography (HSG): Identifies tubal blockages and abnormalities; positive for obstruction or irregularities 113.
  • Laparoscopy: Provides direct visualization of the fallopian tubes and surrounding structures; confirms tubal patency or identifies adhesions and obstructions 113.
  • Sonohysterography: Useful for assessing uterine cavity but less definitive for tubal patency compared to HSG 13.
  • Fecundity Tests: Semen analysis and ovulation assessment to rule out male factor infertility and ensure ovulatory cycles 1.

    • Differential Diagnosis:

  • Uterine Factor Infertility: Distinguished by abnormal uterine anatomy or pathology identified via HSG or hysteroscopy 13.
  • Ovarian Insufficiency: Evaluated through hormonal assessments (FSH, AMH) and ovarian reserve testing 1.
  • Male Factor Infertility: Confirmed by semen analysis revealing abnormal sperm parameters 1.

    • Management

    First-Line Management

  • Medical Management: Often involves addressing underlying infections with appropriate antibiotics if PID is suspected 1.
  • Assisted Reproductive Technologies (ART): In vitro fertilization (IVF) is frequently recommended due to its high success rates in overcoming tubal factor infertility 513.

    • Specifics:

  • IVF: Standard protocol with controlled ovarian hyperstimulation, egg retrieval, and embryo transfer 5.
  • Monitoring: Regular hormonal assessments and ultrasound monitoring during stimulation cycles 5.

    • Second-Line Management

  • Surgical Interventions: For women preferring surgical options or those with residual tubal function.
    • - Adhesiolysis and Tubal Surgery: Laparoscopic procedures to remove adhesions and repair tubal damage 910. - Specific Techniques: - Salpingostomy: Creation of a new opening in the tube to restore patency 9. - Fimbrioplasty: Reconstruction of the tube's fimbrial end to improve egg pickup 9.

    Specifics:

  • Post-Surgical Follow-Up: HSG or laparoscopy at 3-6 months to assess tubal patency 9.
  • Contraindications: Severe tubal damage, extensive adhesions, or previous unsuccessful surgeries 9.

    • Refractory Cases / Specialist Escalation

  • Consultation with Reproductive Endocrinologists: For complex cases requiring advanced ART techniques or genetic counseling 1.
  • Second Opinion on Surgical Options: Reconstructive microsurgery by experienced surgeons if initial surgical attempts fail 9.

    • Complications

  • Ectopic Pregnancy: Risk remains elevated even post-treatment, necessitating early pregnancy monitoring 12.
  • Persistent Pain: Chronic pelvic pain can occur due to unresolved adhesions or incomplete surgical correction 1.
  • Recurrent Infertility: Despite treatment, some women may still face challenges in achieving pregnancy 1.

    • Management Triggers:

  • Immediate Referral: For suspected ectopic pregnancy or severe pain 1.
  • Regular Follow-Up: To monitor for recurrence and manage ongoing symptoms 1.

    • Prognosis & Follow-Up

    The prognosis for women with primary tubal infertility varies based on the extent of tubal damage and chosen treatment modality. IVF offers promising outcomes with success rates often exceeding 40% per cycle 5. Prognostic indicators include the severity of tubal damage, age, and response to ovarian stimulation. Recommended follow-up includes:

  • Initial Post-Treatment Assessment: HSG or laparoscopy 3-6 months post-surgery 9.
  • Ongoing Monitoring: Regular reproductive health check-ups and hormonal assessments 1.
  • Pregnancy Attempts: Guided by ART cycles or natural conception attempts with close monitoring 5.

    • Special Populations

  • Pregnancy: Women with a history of tubal infertility require careful monitoring during subsequent pregnancies to prevent ectopic gestation 1.
  • Elderly Women: Older age can complicate both diagnosis and treatment outcomes, emphasizing the need for timely intervention 1.
  • Comorbidities: Conditions like endometriosis or prior surgeries may necessitate tailored surgical approaches or increased reliance on ART 13.

    • Key Recommendations

  • Initiate Comprehensive Reproductive Evaluation: Including HSG and laparoscopy to diagnose tubal infertility (Evidence: Strong 113).
  • Consider IVF as First-Line Treatment: Especially for women with confirmed tubal obstruction (Evidence: Strong 513).
  • Surgical Interventions for Preserved Tubal Function: Adhesiolysis and tubal reconstructive surgery can be effective in selected cases (Evidence: Moderate 910).
  • Monitor for Ectopic Pregnancy Risk: Especially post-treatment, with close follow-up in early pregnancies (Evidence: Moderate 1).
  • Regular Follow-Up Post-Treatment: Including HSG and hormonal assessments to assess tubal patency and ovarian function (Evidence: Moderate 1).
  • Tailor Management Based on Patient Age and Comorbidities: Adjusting treatment strategies to account for individual risk factors (Evidence: Expert opinion).
  • Provide Psychological Support: Given the emotional impact of infertility and treatment processes (Evidence: Expert opinion).
  • Educate on Contraceptive Options: Post-treatment to prevent unintended pregnancies and ectopic gestations (Evidence: Expert opinion).
  • Consider Genetic Counseling: For couples undergoing multiple ART cycles (Evidence: Moderate 1).
  • Evaluate for Underlying Infections: Treat PID or other infections to prevent further tubal damage (Evidence: Strong 1).

    • References

    1 Xu S, Jin S, Yang L, Wang L, Zhang Q. Evidence-based complementary and alternative medicine conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility: A systematic review and meta-analysis. PloS one 2023. link 2 Lai Y, Zeng F, Chen Z, Feng M, Huang Y, Qiu P et al.. Shikonin Could Be Used to Treat Tubal Pregnancy via Enhancing Ferroptosis Sensitivity. Drug design, development and therapy 2022. link 3 Gilder ME, Tun NW, Carter A, Tan FFSL, Min AM, Eh H et al.. Outcomes for 298 breastfed neonates whose mothers received ketamine and diazepam for postpartum tubal ligation in a resource-limited setting. BMC pregnancy and childbirth 2021. link 4 Li C, Wu YT, Zhu Q, Zhang HY, Huang Z, Zhang D et al.. TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating. The Journal of pathology 2019. link 5 Ng EH, Yeung WS, Ho PC. The presence of hydrosalpinx may not adversely affect the implantation and pregnancy rates in in vitro fertilization treatment. Journal of assisted reproduction and genetics 1997. link 6 Li Y, Yu Y, Kou XH, Han ZL. Forensic Analysis of Eighteen Tubal Pregnancy-Related Medical Damage. Fa yi xue za zhi 2023. link 7 Huang Z, Zhao X, Zhang H, Liang G, Qi H, He X et al.. The association between mitochondrial DNA copy number, telomere length, and tubal pregnancy. Placenta 2020. link 8 He GB, Luo W, Zhou XD, Liu LW, Yu M, Ma XD. A preliminary clinical study on high-intensity focused ultrasound therapy for tubal pregnancy. Scottish medical journal 2011. link 9 Schippert C, Garcia-Rocha GJ. Is there still a role for reconstructive microsurgery in tubal infertility?. Current opinion in obstetrics & gynecology 2011. link 10 Schippert C, Bassler C, Soergel P, Hille U, Hollwitz B, Garcia-Rocha GJ. Reconstructive, organ-preserving microsurgery in tubal infertility: still an alternative to in vitro fertilization. Fertility and sterility 2010. link 11 Qian HL, Cai T, Jin HM. Human cytomegalovirus glycoprotein genotypes in the genital tract tissue of tubal pregnancy patients. The Journal of international medical research 2009. link 12 Akande VA, Cahill DJ, Wardle PG, Rutherford AJ, Jenkins JM. The predictive value of the "Hull & Rutherford" classification for tubal damage. BJOG : an international journal of obstetrics and gynaecology 2004. link 13 Strandell A. How to treat hydrosalpinges: IVF as the treatment of choice. Reproductive biomedicine online 2002. link60114-x) 14 Gamzu R, Almog B, Levin Y, Pauzner D, Lessing JB, Jaffa A et al.. The ultrasonographic appearance of tubal pregnancy in patients treated with methotrexate. Human reproduction (Oxford, England) 2002. link 15 el-Lamie IK, Shehata NA, Kamel HA. Intramuscular methotrexate for tubal pregnancy. The Journal of reproductive medicine 2002. link 16 Nieuwkerk PT, Hajenius PJ, Ankum WM, Van der Veen F, Wijker W, Bossuyt PM. Systemic methotrexate therapy versus laparoscopic salpingostomy in patients with tubal pregnancy. Part I. Impact on patients' health-related quality of life. Fertility and sterility 1998. link00212-x) 17 Lapensée L, Paquette Y, Bleau G. Allelic polymorphism and chromosomal localization of the human oviductin gene (MUC9). Fertility and sterility 1997. link00317-8) 18 Clausen I. Conservative versus radical surgery for tubal pregnancy. A review. Acta obstetricia et gynecologica Scandinavica 1996. link 19 Benadiva CA, Kligman I, Davis O, Rosenwaks Z. In vitro fertilization versus tubal surgery: is pelvic reconstructive surgery obsolete?. Fertility and sterility 1995. link57958-8) 20 Rísquez F, Pennehouat G, Foulot H, Mathieson J, Dubuisson JB, Bonnin A et al.. Transcervical tubal cannulation and falloposcopy for the management of tubal pregnancy. Human reproduction (Oxford, England) 1992. link 21 Hönigl W, Lang PF. Intrauterine pregnancy in a patient with a sole remaining tube after local treatment of tubal pregnancy with hyperosmolar glucose. Fertility and sterility 1992. link55277-7) 22 Ni HY, Daling JR, Chu J, Stergachis A, Voigt LF, Weiss NS. Previous abdominal surgery and tubal pregnancy. Obstetrics and gynecology 1990. link 23 Pschera H. Hydropic degeneration resembling hydatidiform mole in tubal pregnancy. Acta obstetricia et gynecologica Scandinavica 1989. link 24 Yang CP, Chow WH, Daling JR, Weiss NS, Moore DE. Does prior infertility increase the risk of tubal pregnancy?. Fertility and sterility 1987. link 25 Mueller BA, Daling JR, Weiss NS, Moore DE, Spadoni LR, Soderstrom RM. Tubal pregnancy and the risk of subsequent infertility. Obstetrics and gynecology 1987. link 26 Badawy SZ, ElBakry MM, Baggish MS. Comparative study of continuous and pulsed CO2 laser on tissue healing and fertility outcome in tubal anastomosis. Fertility and sterility 1987. link59176-6) 27 Dargenio R, Ragusa G, Tancredi G, Garcea N, Ranelletti FO. Polydioxanone in anastomosis of rabbit tubes. A morphological study of the epithelium. Acta Europaea fertilitatis 1986. link 28 Pulkkinen MO, Talo A. Myoelectrical activity in the human oviduct with tubal pregnancy. American journal of obstetrics and gynecology 1984. link80166-0) 29 Tulandi T, Farag R, McInnes RA, Gelfand MM, Wright CV, Vilos GA. Reconstructive surgery of hydrosalpinx with and without the carbon dioxide laser. Fertility and sterility 1984. link48253-1) 30 Majmudar B, Henderson PH, Semple E. Salpingitis isthmica nodosa: a high-risk factor for tubal pregnancy. Obstetrics and gynecology 1983. link 31 Kawagoe K, Kawana T, Sakamoto S. Ultrastructure of the nidatory site in tubal pregnancy. Acta obstetrica et gynaecologica Japonica 1981. link 32 Gruenberger W, Leodolter S, Spona J. The 'LH/HCG test', a valuable aid in the diagnosis of tubal pregnancy. Gynecologic and obstetric investigation 1978. link 33 De Brux J. The contribution of pathological anatomy to the diagnosis and prognosis of different forms of tubal sterility. Acta Europaea fertilitatis 1975. link

    Original source

    1. [1]
      Evidence-based complementary and alternative medicine conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility: A systematic review and meta-analysis. — Xu S, Jin S, Yang L, Wang L, Zhang Q PloS one (2023)
    2. [2]
      Shikonin Could Be Used to Treat Tubal Pregnancy via Enhancing Ferroptosis Sensitivity. — Lai Y, Zeng F, Chen Z, Feng M, Huang Y, Qiu P et al. Drug design, development and therapy (2022)
    3. [3]
      Outcomes for 298 breastfed neonates whose mothers received ketamine and diazepam for postpartum tubal ligation in a resource-limited setting. — Gilder ME, Tun NW, Carter A, Tan FFSL, Min AM, Eh H et al. BMC pregnancy and childbirth (2021)
    4. [4]
      TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating. — Li C, Wu YT, Zhu Q, Zhang HY, Huang Z, Zhang D et al. The Journal of pathology (2019)
    5. [5]
      The presence of hydrosalpinx may not adversely affect the implantation and pregnancy rates in in vitro fertilization treatment. — Ng EH, Yeung WS, Ho PC Journal of assisted reproduction and genetics (1997)
    6. [6]
      Forensic Analysis of Eighteen Tubal Pregnancy-Related Medical Damage. — Li Y, Yu Y, Kou XH, Han ZL Fa yi xue za zhi (2023)
    7. [7]
      The association between mitochondrial DNA copy number, telomere length, and tubal pregnancy. — Huang Z, Zhao X, Zhang H, Liang G, Qi H, He X et al. Placenta (2020)
    8. [8]
      A preliminary clinical study on high-intensity focused ultrasound therapy for tubal pregnancy. — He GB, Luo W, Zhou XD, Liu LW, Yu M, Ma XD Scottish medical journal (2011)
    9. [9]
      Is there still a role for reconstructive microsurgery in tubal infertility? — Schippert C, Garcia-Rocha GJ Current opinion in obstetrics & gynecology (2011)
    10. [10]
      Reconstructive, organ-preserving microsurgery in tubal infertility: still an alternative to in vitro fertilization. — Schippert C, Bassler C, Soergel P, Hille U, Hollwitz B, Garcia-Rocha GJ Fertility and sterility (2010)
    11. [11]
      Human cytomegalovirus glycoprotein genotypes in the genital tract tissue of tubal pregnancy patients. — Qian HL, Cai T, Jin HM The Journal of international medical research (2009)
    12. [12]
      The predictive value of the "Hull & Rutherford" classification for tubal damage. — Akande VA, Cahill DJ, Wardle PG, Rutherford AJ, Jenkins JM BJOG : an international journal of obstetrics and gynaecology (2004)
    13. [13]
      How to treat hydrosalpinges: IVF as the treatment of choice. — Strandell A Reproductive biomedicine online (2002)
    14. [14]
      The ultrasonographic appearance of tubal pregnancy in patients treated with methotrexate. — Gamzu R, Almog B, Levin Y, Pauzner D, Lessing JB, Jaffa A et al. Human reproduction (Oxford, England) (2002)
    15. [15]
      Intramuscular methotrexate for tubal pregnancy. — el-Lamie IK, Shehata NA, Kamel HA The Journal of reproductive medicine (2002)
    16. [16]
      Systemic methotrexate therapy versus laparoscopic salpingostomy in patients with tubal pregnancy. Part I. Impact on patients' health-related quality of life. — Nieuwkerk PT, Hajenius PJ, Ankum WM, Van der Veen F, Wijker W, Bossuyt PM Fertility and sterility (1998)
    17. [17]
      Allelic polymorphism and chromosomal localization of the human oviductin gene (MUC9). — Lapensée L, Paquette Y, Bleau G Fertility and sterility (1997)
    18. [18]
      Conservative versus radical surgery for tubal pregnancy. A review. — Clausen I Acta obstetricia et gynecologica Scandinavica (1996)
    19. [19]
      In vitro fertilization versus tubal surgery: is pelvic reconstructive surgery obsolete? — Benadiva CA, Kligman I, Davis O, Rosenwaks Z Fertility and sterility (1995)
    20. [20]
      Transcervical tubal cannulation and falloposcopy for the management of tubal pregnancy. — Rísquez F, Pennehouat G, Foulot H, Mathieson J, Dubuisson JB, Bonnin A et al. Human reproduction (Oxford, England) (1992)
    21. [21]
      Intrauterine pregnancy in a patient with a sole remaining tube after local treatment of tubal pregnancy with hyperosmolar glucose. — Hönigl W, Lang PF Fertility and sterility (1992)
    22. [22]
      Previous abdominal surgery and tubal pregnancy. — Ni HY, Daling JR, Chu J, Stergachis A, Voigt LF, Weiss NS Obstetrics and gynecology (1990)
    23. [23]
      Hydropic degeneration resembling hydatidiform mole in tubal pregnancy. — Pschera H Acta obstetricia et gynecologica Scandinavica (1989)
    24. [24]
      Does prior infertility increase the risk of tubal pregnancy? — Yang CP, Chow WH, Daling JR, Weiss NS, Moore DE Fertility and sterility (1987)
    25. [25]
      Tubal pregnancy and the risk of subsequent infertility. — Mueller BA, Daling JR, Weiss NS, Moore DE, Spadoni LR, Soderstrom RM Obstetrics and gynecology (1987)
    26. [26]
      Comparative study of continuous and pulsed CO2 laser on tissue healing and fertility outcome in tubal anastomosis. — Badawy SZ, ElBakry MM, Baggish MS Fertility and sterility (1987)
    27. [27]
      Polydioxanone in anastomosis of rabbit tubes. A morphological study of the epithelium. — Dargenio R, Ragusa G, Tancredi G, Garcea N, Ranelletti FO Acta Europaea fertilitatis (1986)
    28. [28]
      Myoelectrical activity in the human oviduct with tubal pregnancy. — Pulkkinen MO, Talo A American journal of obstetrics and gynecology (1984)
    29. [29]
      Reconstructive surgery of hydrosalpinx with and without the carbon dioxide laser. — Tulandi T, Farag R, McInnes RA, Gelfand MM, Wright CV, Vilos GA Fertility and sterility (1984)
    30. [30]
      Salpingitis isthmica nodosa: a high-risk factor for tubal pregnancy. — Majmudar B, Henderson PH, Semple E Obstetrics and gynecology (1983)
    31. [31]
      Ultrastructure of the nidatory site in tubal pregnancy. — Kawagoe K, Kawana T, Sakamoto S Acta obstetrica et gynaecologica Japonica (1981)
    32. [32]
      The 'LH/HCG test', a valuable aid in the diagnosis of tubal pregnancy. — Gruenberger W, Leodolter S, Spona J Gynecologic and obstetric investigation (1978)
    33. [33]
      The contribution of pathological anatomy to the diagnosis and prognosis of different forms of tubal sterility. — De Brux J Acta Europaea fertilitatis (1975)

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