Accepted Manuscript

Sperm Washing with Intrauterine Insemination and Preexposure Prophylaxis: An

Innovative Approach to Treating Hiv-Serodiscordant Couples

L.Z. Safier, L.C. Grossman, M.V. Sauer, N.C. Douglas

PII: S0002-9378(17)30365-4
DOI: 10.1016/j.ajog.2017.02.038
Reference: YMOB 11558

To appear in: American Journal of Obstetrics and Gynecology

Received Date: 31 December 2016

Revised Date: 13 February 2017
Accepted Date: 23 February 2017

Please cite this article as: Safier LZ, Grossman LC, Sauer MV, Douglas NC, Sperm Washing with
Intrauterine Insemination and Preexposure Prophylaxis: An Innovative Approach to Treating Hiv-
Serodiscordant Couples, American Journal of Obstetrics and Gynecology (2017), doi: 10.1016/
j.ajog.2017.02.038.

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 ACCEPTED MANUSCRIPT

SPERM WASHING WITH INTRAUTERINE INSEMINATION AND PREEXPOSURE

PROPHYLAXIS: AN INNOVATIVE APPROACH TO TREATING HIV-
SERODISCORDANT COUPLES

L.Z. Safier, L.C. Grossman, M.V. Sauer, N.C. Douglas

Columbia University Medical Center, New York, NY

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The authors report no conflict of interest

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Corresponding Author
Nataki Douglas, M.D., Ph.D.

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Columbia University Medical Center
nd2058@cumc.columbia.edu

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Objective: Sperm washing (SW) with intrauterine insemination (IUI) has been advocated as a

safe, efficacious way to achieve pregnancy and reduce the risk of human immunodeficiency

virus (HIV) transmission in HIV-serodiscordant couples in which the male partner is HIV-

infected 1-3. HIV is present as free virions in seminal plasma and as cell-associated virus in non-

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spermatic cells 4. Utilizing sperm concentrate prepped free of these cell types provides safety

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from sexual transmission 3. In the United States (US), few centers provide fertility care for HIV-

serodiscordant couples. SW with intracytoplasmic sperm injection (ICSI) of sperm into mature

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eggs harvested for in vitro fertilization (IVF) has been utilized as a first line assisted

reproduction treatment, although this method is often cost prohibitive and requires dedicated IVF

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laboratory equipment 2. The US Department of Health and Human Services recommends
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preexposure prophylaxis (PrEP) anti-retroviral therapy for sexually active couples to reduce

infection transmission rates5. For HIV-serodiscordant couples in which the female partner is
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seronegative, we initiated an innovative therapy of SW-IUI combined with PrEP to further

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reduce risk of HIV transmission.

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Study Design: Eleven HIV-serodiscordant couples were treated with SW-IUI at Columbia
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University Medical Center from 1/1/2014 – 10/2016 (IRB-AAAQ7656). All couples reported

safe-sex practices with condoms. The pretreatment assessment for couples considering SW-IUI
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is outlined in Table 1. Selected couples gave informed written consent and were eligible to
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undergo a maximum of six attempts of SW-IUI. Ovulatory women underwent natural cycles and

anovulatory women underwent ovulation induction with clomiphene citrate. Superovulation

using clomiphene citrate was performed at the physician’s discretion for women ≥ 35 years (yrs)

of age or women who had previously failed IUI cycles. SW utilized techniques of gradient
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centrifugation and sperm migration (swim-up)3. Motile sperm were collected for IUI3. IUI was

performed 12 hours after a luteinizing hormone surge or 36 hours after administration of

Ovidrel®, recombinant human choriogonadotropin alfa (hCG) trigger. Women were prescribed

Truvada® (emtricitabine and tenofovir disoproxil fumarate) as PrEP the day before, day of and

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day after the IUI. Female HIV testing was performed at each cycle start, at completion of

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treatment if not pregnant, and every 3 months throughout resultant pregnancies.

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Results: Eleven couples completed 28 cycles of SW-IUI, with 6 cycles resulting in pregnancy.

The median female age was 34 yrs (interquartile range 31.5 – 35 yrs). Median pre-wash and

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post-wash total motile sperm counts were higher in cycles that achieved pregnancy as compared
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to those without pregnancy (pre-wash: 92.8 vs 21.5 million, P<0.05; post-wash: 2.0 vs 1.0

million, P<0.10). Both natural cycles (3/6) and cycles stimulated with clomiphene citrate (3/6)
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resulted in pregnancy. Women who achieved pregnancy did so during the 1st or 2nd SW-IUI
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cycle. All women remained HIV negative at follow-up testing six months later.
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Conclusion: SW-IUI with PrEP appears to be a safe and effective method of conception for
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well-selected HIV-serodiscordant couples with a fecundabilty rate of 21.4%. Reduced cost and

resource utilization associated with this therapy may enable other centers to offer SW-IUI,
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ultimately increasing access for resource poor communities.

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References:
1. ZAFER M, HORVATH H, MMEJE O, et al. Effectiveness of semen washing to prevent
human immunodeficiency virus (HIV) transmission and assist pregnancy in HIV-
discordant couples: a systematic review and meta-analysis. Fertil Steril 2016;105:645-55
e2.
2. SAVASI V, MANDIA L, LAORETI A, CETIN I. Reproductive assistance in HIV
serodiscordant couples. Hum Reprod Update 2013;19:136-50.

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3. SEMPRINI AE, MACALUSO M, HOLLANDER L, et al. Safe conception for HIV-discordant
couples: insemination with processed semen from the HIV-infected partner. Am J Obstet
Gynecol 2013;208:402 e1-9.

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4. MERMIN JH, HOLODNIY M, KATZENSTEIN DA, MERIGAN TC. Detection of human
immunodeficiency virus DNA and RNA in semen by the polymerase chain reaction. J
Infect Dis 1991;164:769-72.

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5. CENTERS FOR DISEASE C, PREVENTION. Interim guidance for clinicians considering the
use of preexposure prophylaxis for the prevention of HIV infection in heterosexually
active adults. MMWR Morb Mortal Wkly Rep 2012;61:586-9.

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Table 1: Medical and reproductive pretreatment requirements for SW-IUI combined with
PrEP
Medical Reproductive
Female
HIV negative status Age ≤ 40 years
Hepatitis B surface antigen and Hepatitis C Normal ovarian reserve studies with anti-

antibody negative with documented Hepatitis B
immunity
Normal laboratory parameters for kidney, liver
and gastrointestinal function
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Müllerian hormone (AMH) > 1.0 ng/mL*
Normal prolactin and thyroid levels

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No medical contraindications to PrEP Hysterosalpingogram with patent fallopian
tubes
Male

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Under active medical surveillance by an 2 semen analyses
infectious disease specialist
Adherent to a highly active anti-retroviral Calculated total motile sperm counts ≥ 10
therapy regimen million sperm

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Stable HIV disease for ≥ 3 months
CD4 counts ≥ 250 cells/mm3
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Undetectable plasma HIV RNA viral counts (<
50 copies/mL)
*AMH Gen II enzyme-linked immunosorbent assay (Beckman Coulter)
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