Fertility Management in HIV Discordant Couple

Dr. Neelam Ohri. MS, FICOG,Medical Director

Biologic Parenthood in HIV Discordant Couple

• HIV is a serious but manageable chronic disease

• The largest group affected (86%) are persons of reproductive age (15–44 years old)

• HIV-serodiscordant couples are actively seeking reproductive assistance for biologic parenthood.

Improved Understanding and Treatment

During last two decades understanding and treatment of HIV-infected persons and lab techniques for the preparation of virus-free sperms have improved substantially

Current treatments for HIV can limit the risk of viral transmission to the partner and offspring

Ethical Issues with Infertility treatment

• Infertility treatment in Sero discordant couple

Sero concordant couple• Knowingly conceiving a child who may be born

with HIV• HIV testing for couples seeking fertility assistance• Potential risks to the health- care providers• Improving access to infertility care for HIV-

infected individuals• Providing third party assisted reproductive

services

Issues to be addressed

• Potential deleterious effects of HIV-1 infection on fertility

• The impact of ARV therapy on fertility.• The impact of co-morbidities (e.g.STDs, drug

abuse) on fertility.

For Couples Who Want to Conceive Discordant or Concordant

• Expert consultation is recommended (AIII).• Partners should be screened and treated for genital

tract infections (AII). • The HIV-infected partner(s) should attain maximum

viral suppression before attempting conception (AIII).

• PrEP for uninfected partner may offer an additional tool to reduce the risk of sexual transmission (CIII).

(CDC recommendations)

Male infertility and HIV

Since 1987, > 4000 published data for processed spermatozoa from HIV-seropositive menHIV and ARVs impact on semen parameters and sexual function• Controversial results: may be associated with borderline semen

abnormalities. For others, no impact. Semen parameters correlate positively with CD4 counts

• Erectile and ejaculatory dysfunction is estimated to affect 60% of men with advanced disease

HIV transmission rate to an uninfected partner Approximately 1 in 500–1,000 episodes of unprotected intercourse. The risk increases dramatically - if infected partner's viral load is high or - the uninfected partner has a concomitant

genital infection,

Infertility Treatment in discordant couple (Male)

Semen analysis is recommended, If abnormalities are present, the uninfected female partner may be exposed unnecessarily

Ways in which conception can occur:

1.Timed unprotected intercourse: Using condoms except at the time of ovulation appear to reduce, but not eliminate, the risk of seroconversion

The seroconversion rate was 4.3% of 92 HIV-uninfected women with HIV- infected partners. Two of the women in that study seroconverted during pregnancy, and another 2 converted in the postpartum period.

This practice is not recommended

- Cohen MS et all.N Engl J Med 2011;365:493-505

Infertility Treatment in discordant couple (Male)

2. ARV therapy during the time conception is attempted and PrEP in the uninfected female partner during the.

In a study of 46 serodiscordant couples, the female was treated with oral tenofovir, (One dose was taken at LH peak and a second 24 hours later) none of the women became infected with HIV and pregnancy rates reached 75% after 12 attempts.

This and other studies indicate that adherence to clinical protocols is essential for preventing transmission.

The US FDA has approved only daily dosing of combination tenofovir and emtricitabine for PrEP

3. Use of donor sperms

Infertility Treatment in discordant couple (Male)

4.The use of sperm preparation techniques coupled with either IUI or IVF with ICSI

Based on the principal that HIV virus is present in seminal plasma and seminal leucocytes but is not associated with sperms. Sperms lack CD4 and CCR5 receptors on their surface that allow the virus to bind with and enter the cell.

Infertility Treatment in discordant couple (Male)

IUI-IVF ICSI• IUI or ICSI has proven to be highly effective in avoiding

seroconversion of uninfected women and offspring. • HAART can reduce the viral burden in a person's serum and

semen. • PrEP may reduce further the susceptibility of the uninfected

female partner.• Some centers have also adopted testing of sperm by using a

PCR assay (RNA)after preparation, but the utility and effectiveness of this added step has been questioned by other centers that have eliminated PCR from their protocols.

Sperm Preparation TechniqueSperm Washing

Sperm Preparation Techniques

Infertility Treatment in discordant couple (Male)

IVF with ICSI • Recent data on the use of ICSI are

promising in terms of avoiding transmission to uninfected women.

• In a 10-year retrospective review of a program stated no female seroconversions and no infections in any of the offspring. Sauer MV et all. Fertil Steril 2009;91:2455-60

HIV infection and Female Reproductive Potential

• Fertility is 25– 40% lower • Systemic illness, stress, weight loss may impact

reproductive potential• Co-morbid conditions, PIDs, higher rates of

concomitant M. hominis, candida, streptococcal, HPV and HSV-2

• HIV infection has contributed to a worldwide increase in the incidence of TB

• ARVs may adversely affect reproductive potential via damage to mitochondrial biogenesis in gametes.

Infertility Treatment in Discordant couple (Female)

• Assess the reproductive potential of female• Ways for conception:• 1. IUI by using homologous insemination will suffice in order to prevent horizontal infection.

• 2. Self-inseminate with the partner’s sperm during the periovulatory period is other option. Condom use should be advised at all times.

• 3. Timed intercourse, assuring suppressed viral load of woman

and the uninfected male is taking PrEP. This option is not as safe as homologous IUI, it does represent an alternative option for select couples.

Infertility Treatment in Discordant couple (Female)

• The resulting pregnancy may still pose some risk to the HIV- infected woman and her child• Opportunistic infections occurring during

pregnancy • Invasive procedures (Amniocentesis and

CVB), may also increase risk of transmission to the fetus.

• In addition there is variable risk of vertical transmission

Infertility Treatment in Concordant Couples

• Assessment of the fertility potential

• Both should be on cART with maximum viral suppression before attempting conception.

• The risk of HIV superinfection or infection with a resistant virus is negligible when both partners are on cART and have fully suppressed plasma viral loads.

Ethical Issues Raised by Knowingly Risking the Birth of a Child with HIV

• The risk of vertical transmission can be greatly reduced but not completely eliminated.

• This raises ethical issues concerning the scope of freedom to reproduce.

• The ethical issues are similar to carriers of an autosomal recessive disease, where the risk of transmitting the disease through natural conception cannot be reduced below 25%, whereas the risk of HIV transmission can be reduced to a substantially lower number—in some cases, to less than 2%.

Testing Infertile Couples for HIV

• The ACOG recommends that ObGy routinely screen their female patients aged 19–64 years for HIV regardless of individual risk factors

• Repeated testing is recommended for those with ongoing risk for HIV infection

• ART Regulation Bill 2010,The Bank shall ensure that the sperm / egg donor, Surrogate is free from HIV and repeated every 6 months and only frozen thawed samples should be provided

Laboratory Cross-contamination of the gametes or

embryos , Myths and Realities• Numerous ART centers worldwide equipped with separate

lab space and provide separate storage tanks for freezing infected gametes and embryos

• There are no reports of HIV infection of lab personnel resulting from processing the gametes/embryos adopting standard universal precautions.

• Cross-contamination of the gametes or embryos of other couples in the same laboratory has also not been reported.

• To avoid even the possibility of cross-contamination, the ASRM Practice Committee recommends that samples from a viral carrier be processed in a separate laboratory or designated space within the main laboratory, utilizing a dedicated storage tank.

HIV AND THE HEALTH PROFESSIONAL

Health professionals may be legally, as well as ethically, obligated to provide requested reproductive assistance, unless they can show that they lack the skill and facilities to treat these patients safely

Clinics without sufficient resources to offer care should assist in referral to providers equipped to manage such patients.

• Despite improved outcomes in the use of sperm washing access to these reproductive technologies fo seropositive individuals is extremely limited.

• Fewer than 3% of US ART practices registered with the Society for ART provide service to these couples

HIV AND THE HEALTH PROFESSIONAL

THIRD-PARTY ASSISTED REPRODUCTION FOR HIV-INFECTED INTENDED PARENTS

• Disclosure of an intended parent's HIV status to gamete donors or surrogate should commensurate with principles of informed consent.

• When an intended parent's HIV status poses no medical risk to gestational carriers, it should be regarded the same as any chronic health condition.

CONCLUSION

• The potential for HIV-infected persons to live long and healthy lives, have uninfected children, and not transmit the virus to their partners has resulted in increasing numbers of individuals to seek out optimal means for creating biologic families.

• Evidence-based practice and social justice suggest that our field should increase access to care for HIV-serodiscordant couples

• Fertility treatment is a safe option for HIV-discordant couples, and may be safer than attempted natural conception.

CONCLUSION

• Sperm washing should only be carried out in dedicated units using a multidisciplinary approach ensuring adequate pre-conceptional counseling, detailed sexual health and fertility assessment and careful monitoring of the woman’s HIV status during treatment and pregnancy.

• Clinics without sufficient resources to offer care should assist in referral to providers equipped to manage such patients.

• Thank you!