Tuberculosis And IVF Results | Jindal IVF

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Tuberculosis And IVF Results  

• Umesh N Jindal
• Jindal IVF and Sant memorial Nursing Home,
  Chandigarh

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FGTB effect of fertility and IVF outcome
Phenotypes of TB
Site of involvement
NO apparent genital involvement of pulmonary or
other extrapulmonary TB
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Various questions?

• Is there a difference in IVF outcome among
  various phenotypes of GTB?
• Have the IVF results in GTB improved and
  comparable to other aetiologies over years?
• Does TB has impact on ovarian reserve?
• What to do with hydrosalpinges in genital TB?
• Does TB reduces endometrial receptivity even
  without visible signs of endometrial damage?
• What are the risks of untreated TB undergoing
  IVF?
• What can be done for patients with severe ovarian
  or endometrial involvement ?

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1.Is there a difference in IVF outcome in various
phenotypes?
sequelae

• Retrospective analysis of 180 patients who
  received ATT on any grounds and underwent IVF
  January 2016-December, 2020.
• Donor oocyte, surrogacy and age gt40 years
  excluded
• Outcome measures- 1) Cumulative CPR
  and 2)Cumulative LBR

latent
extragenital
clinical
Kaur P et al .JISNH thesis data
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Table 26 CCPR in various phenotypes
Phenotype Phenotype Phenotype Phenotype Total
Extragenital Subclinical Clinical Sequelae
number 11/21 30/41 52/113 2/5 95
percentage 52.4 73.2 45.5 40.0 52.5
Kaur P et al .JISNH thesis data
Plt 0.023
Table 27 CLBR in various phenotypes
Phenotype Phenotype Phenotype Phenotype Total
Extragenital Subclinical Clinical Sequelae
number 11/21 28/41 50/113 2/5 91
percentage 52.4 68.29 44.2 40.0 50.5
Kaur P et al .JISNH thesis data
Plt 0.066
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Number of attempts and ectopic pregnancy
ET Rank Phenotype Phenotype Phenotype Phenotype Total
Extragenital Subclinical Clinical Sequelae
1 8/21 (38.1) 19/41 (46.3) 28/113 (24.1) 0/5 (0.0) 55/180 (30.2)
2 2/21 (9.5) 8/41 (19.5) 14/113 (12.5) 2/5 (40.0) 25/180 ( 14.2)
3 1/21 (4.8) 1/41 (2.4) 8/113 (7) O/5 (0.0) 8/180 (4.5)
Plt 0.110

• An ectopic pregnancy rate of 2.2 was observed in
  our study which could not be correlated to any
  phenotype.

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Overall CCPR52.5 and CLBR50.5
Clinical group CCPR45.5 and CLBR44.2
Kaur P et al .JISNH thesis data
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Phenotype 1 IVF outcome in extra-genital TB 

• The untreated PTB group had significantly lower
  CPR(31.7 vs. 38.1) and LB(23.8 vs. 30.6)
  rates than the non-PTB group (both P lt 0.001). RR
  0.88 and increased miscarriage 4.19 and
  decreased LB 45.
• Outcome in treated pulmonary TB was similar Yan
  Gai et al Biomed Environ Sci 2021

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Phenotype 2 Sub-Clinical GTB
n 119 PCR ve 52 PCR -ve 67 Median Time to
pregnancy PCR ve 7.0 (CI 5.8-8.2) PCR-ve 10.0
(CI 6.8-13.2)
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IVF outcome with treatment of early GTB
2012
EB PCR Pregnancy Treatment Taken Treatment Taken Treatment Taken Treatment Taken Treatment Taken Treatment Taken Total Total
Nil Nil IUI IUI IVF IVF
Positive No No No No
Pearsons chi-square plt.154 Yes 52 74.3 30 44.8 19 59.4 101 59.8
Pearsons chi-square plt.154 No 18 25.7 37 55.2 13 40.6 68 40.2
Pearsons chi-square plt.154 Sub Total 70 41.4 67 40 32 19.6 169 100
Negative Yes 67 72 67 49.3 33 73.3 167 60.9
Pearsons chi-square plt.274 No 26 28 66 50.7 12 26.7 107 39.1
Pearsons chi-square plt.274 Sub Total 93 33.9 136 49.6 45 16.4 274 100
Biochemical pregnancy rate
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• Post ATT, women with latent GTB Better
  implantation rate (26.8 vs. 17.5 P 0.004)
  and higher IVF pregnancy rate (68.6 vs. 48.5
  P 0.001)

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Group 4 IVF results in healed TB
27/5027
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Quiestion2 Have the IVF results in GTB improved
over years and comparable to other aetiologies ?
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What has changed over these seven decades after
independence ?

• Epidemiology- NTEP
• Diagnostic methods- addition of molecular and
  imaging techniques
• Effective short course chemotherapy
• Endoscopic surgery
• IVF- revolution in pregnancy rates
• Future -Regenerative medicine/uterine transplant-
  most difficult cases with permanent damage to
  uterus

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• Pelvic TB usually secondary to Pulmonary TB
  exposure 5-10 years earlier
• Incidence of TB is decreasing _at_ 2.2/year
  (Damnetya et al 2021)
• Is genital TB also decreasing at the same
  rate?(Index of suspicion depends upon prevalence
  of a disease)

incidence
mortality
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Trends in IVF success rate

• Bapna et al 2005- 4.2-30.7 delivery rate
• Grace A 2017- 11.8 to 23 CPR

Kaur P et al .JISNH thesis data
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IVF results with history of TB at JISNH
(Unpublished)
period Tuberculosis Tuberculosis Tuberculosis others others others Total Total Total
period N CP CPR N CP CPR N CP CPR
2012-14 224 76 33.93 584 254 43.49 808 330 40.84
2015- 18 125 62 49.60 650 368 56.62 775 430 55.48

• The percentage contribution of cases undergoing
  IVF decreased from 224/808 (27.72) in 12-14 to
  125/775 (16.13) in year15-18
• CPR improvement was 32.92 in cases with history
  of ATT as compared to overall improvement of
  26.39

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Question3 Does TB has impact on ovarian reserve?

• Women undergoing IVF with OD were excluded.
• Patients with clinical TB and sequelae required
  longer stimulation Kaur P et al JISNH thesis
  data
• Patients with subclinical TB had significantly
  lower AMH Median (IQR) 2 (0.9, 4.1) ng/ml vs
  2.8 (1.3, 5) ng/ml P 0.01 and AFC Median
  (IQR) 7 (5, 11) vs 8 (5, 14) P lt 0.001.
• Post ATT, women with latent GTB yielded fewer
  oocytes (9.3 7.6 vs. 10.9 8.1 P 0.01)
  Jirge et 2018

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Question4 What to do with hydrosalpinges in
genital TB?

1. Cure of pelvic tuberculosis is achieved more
   quickly with surgery than with ATT alone
2. GTB diagnosed at Surgery- Bilateral salpingectomy
   followed by ATT in presence of hydrosalpinges.
   Conservation of tubes should be weighed against
   risk of repeat surgery for removal of
   hydrosalpinges if IVF is required
3. Otherwise no surgery and no drainage. Appropriate
   biopsies and samples for microbiology to be
   collected. George
   Sheafer 1956

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Melo P et al Surgical treatment for tubal disease
in women due to undergo in vitro fertilisation.
Cochrane Database of systematic Reviews 2020,
Issue 10. Art. No. CD002125
2020
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Effects of salpingectomy and antituberculosis
treatments on fertility results in patients with
genital tuberculosis. Caliskan et al. J Obstet
Gynaecol Res . 2014

• The salpingectomy group required longer
  stimulation(10.42.3 vs 9.21.8 P0.048) but
  similar M2 oocytes, embryos transferred.
• CPR was higher in group 1 (37.5, 12/32 vs 23.8,
  5/21 P0.306)
• Ongoing pregnancies per ET, spontaneous abortion
  rates before 20 weeks of gestation and take-home
  baby rates were higher in group 1 compared to
  group 2 (15.5, 12/77 vs 6.6, 3/45 P0.150
  28.1, 9 vs 23.8, 5 P0.600 9, 3 vs 0
  P0.160, respectively).

2020
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Question5 Does TB reduces endometrial
receptivity with visible or without visible signs
of endometrial damage?
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(Fertil Steril 2016

• Result(s) Significantly reduced levels of
  endometrial receptivity markers LIF, LIFR, and
  pSTAT3 were observed in endometrium of women with
  dormant GTB as compared with controls.
• A similar trend was observed under in vitro
  conditions with decreased level of phosphorylated
  STAT3 in HSP65-treated hESC.
• However, no change in the expression of
  endometrial receptivity markers under in vitro
  conditions was observed.

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Studies from AIIMS Delhi

• Early ATT improved menstrual cycle, endometrial
  thickness and reduced incidence of grade I
  adhesions. Advanced stages did not show any
  improvement. Effect of Antitubercular Therapy on
  Endometrial Function in Infertile Women with
  Female Genital Tuberculosis. JB Sharma et al.
  Infect Disord Drug Targets 2016

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.In vitro fertilization outcome in women with
endometrial tuberculosis and tubal
tuberculosisWenrong Dai et al  2020
Sep36(9)819-823

• Conclusions  IVF/ICSI-ET remains the most
  optimal method for the treatment of female
  infertility associated with GTB.
• However, patients with endometrium tuberculosis
  showed significantly reduced endometrial
  thickness, high-quality embryos rate
  fertilization, implantation and cumulative
  pregnancy rates controls (p lt .05).
• CPR and pregnancy outcome between tubal and
  non-TB patients was similar

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Question6 What are the risks of untreated TB
undergoing IVF?

• Congenital TB
• Congenital spinal Tuberculosis associated with
  asymptomatic endometrial tuberculosis A rare
  case report. Kumar A et al 2008
• Congenital tuberculosis after in vitro
  fertilization suggestion for tuberculosis tests
  in infertile women in developing countries.
  Xiaoling Zhang 2018

• Flare Up of TB
• Postoperative flare-up of genital tuberculosis a
  clinical reality. Singh N et al
• Pelvic tuberculosis reactivated by in vitro
  fertilization egg collection? Annamrahu H et al F
  S 2008

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(Fertil Steril Rep 2022328591)
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Question 7 What can be done for patients with
severe ovarian or endometrial involvement ?

• Rule out endometrial damage due to TB, adhesions,
  persistent hydrosalpinges
• Hysteroscopic adhesiolysis is the only option but
  success come only with early or less severe
  damage
• Salpingectomy and ATT may improve endometrium in
  some cases
• Some of very thin endometrium cases may also
  conceive
• Surrogacy a very reasonable option
• Stem cells and Uterine transplant are newer
  options

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Conclusion

• Subclinical GTB has significantly higher success
  rate than other types, Treated pulmonary TB has
  no impact, clinical TB success is comparable to
  other diagnosis and many women with sequelae may
  not be suitable for IVF
• Overall incidence of TB has decreased and IVF
  results in TB have improved in parallel with
  other aetiologies
• Yes, GTB even in subclinical form has impact on
  ovarian reserve and ovarian function improves
  after ATT
• Bilateral salpingectomy followed by ATT in
  presence of hydrosalpinges. Conservation of tubes
  should be weighed against risk of repeat surgery
  for removal of hydrosalpinges if IVF is required

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Various questions?

• Yes, endometrial receptivity is reduced even in
  untreated subclinical TB and in clinical GTB
  success rates reduced as compared to tubal
  involvement.
• Congenital TB and flare of TB after surgery or
  ovum pick up
• Adhesiolysis, surrogacy, stem cells and uterine
  transplant are some options

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I can be a mother !!!