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Assisted Reproduction Techniques


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       Mark V. Sauer and Shelley Dolitsky

       Department of Obstetrics, Gynecology and Reproductive Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

       Case History 1: An HIV‐serodiscordant couple wished to have a child. The man had a history of intravenous drug use as a teenager and contracted HIV from an infected needle. He claims to have discontinued all illicit drug use 15 years ago and is compliant with his highly active antiretroviral therapy (HAART). His viral load was undetectable, and his CD4 count was 800 cells/mm3 at a recent visit to his primary care physician. The couple’s infertility evaluation was entirely unremarkable. Intrauterine insemination (IUI) of washed/swim up prepared sperm was performed on his partner during her natural spontaneous ovulatory cycles using a previously frozen semen specimen. Prior to the sample being frozen and used for treatment, an aliquot of semen was tested for the presence of detectable HIV RNA using a nucleic acid sequence‐based amplification (NASBA) method and found to be negative. The patient conceived on her third attempt with IUI. Both mother and child were HIV‐seronegative at delivery and three months postpartum.

       Case History 2: An HIV‐seropositive male wished to have a child. He was medically stable and taking antiretroviral therapy resulting in undetectable viral loads and a CD4 count above 400 cells/mm3. His wife takes pre‐exposure prophylaxis (PrEP) daily. They chose to have timed unprotected sexual intercourse using ovulation kits but had no success after 6 months attempting pregnancy. At the time of his infertility evaluation, he was noted to have low testosterone levels and oligo‐astheno‐teratospermia. He was prescribed clomiphene citrate, 25 mg daily for 25 days, followed by a break of 5 days, for 6 months. He was advised to repeat the semen analysis in six months, with some improvement in all parameters noted on repeat testing. However, the specimen overall remained below normal counts and morphology. A decision was made to proceed with intra‐cytoplasmic sperm injection (ICSI), which was performed several weeks later following density gradient sperm washing with swim up on the semen sample. The patient conceived following the transfer of one blastocyst. Both mother and child were HIV‐seronegative at delivery.

      It is estimated that globally nearly 40 million people are infected and living with HIV with 1.7 million new infections reported annually [1]. The majority of cases occur in men who are young, and many will later desire to have children. The advent of effective antiretroviral therapies allows infected individuals the opportunity to live relatively normal lives and has dramatically improved life expectancy. However, the known risk of sexual transmission of HIV endangers their partners and offspring unless measures to safeguard against infection, such as condom only sex, are practiced. Past reports of estimated male‐to‐female transmission risk ranged from 1 in 100 to 1 in 200 acts of intercourse [2], but the risk can be decreased substantially if the unaffected partner is prescribed pre‐exposure prophylaxis (PrEP) therapy [3–5].

      Since 1992 a relatively simple method for processing the semen of HIV‐seropositive men has been used to separate the seminal plasma and nonmotile cellular components (e.g. lymphocytes and other CD4 receptor positive cell lines) from the motile spermatozoa [6]. HIV is a retrovirus that primarily infects T lymphocytes and other immune cells and is also present as free virus in semen and other body fluids. Spermatozoa do not express CD4, CCR5 and CXCR4 receptors and therefore are unlikely to be a significant vector of HIV infection [7].

      “Sperm washing” of HIV‐seropositive men is best performed by laboratories specially equipped to handle virally infected patients. Samples are prepared in class II biologic hoods located in a separate area outside of the embryology laboratory. Fresh samples used for IUI or ICSI are first processed by centrifugation in a discontinuous density gradient. Then, two different methods have been utilized to separate the sperm from the seminal plasma. In the originally described method, the sperm pellet is resuspended and centrifuged again before preparation with a final swim up stip. Thus, the specimen is “double washed with swim up” prior to use [8]. A different method has also been proposed using a polypropylene tube insert during the centrifugation step, thus eliminating the need for the “double washed swim up” step. The latter method led to a 98.1% and 100% effectiveness in eliminating HIV‐DNA and HIV RNA from semen samples, respectively [9,10].

      Based upon surveys of HIV‐seropositive individuals attending medical clinics, approximately 15–30% of HIV‐infected patients demonstrate an interest in reproductive care [11,12]. A multidisciplinary team approach to the management of HIV‐seropositive patients is advocated. Consultation with the infectious disease specialist treating the infected patient is vitally important to understand the general health status of the prospective patient. Individuals should be medically stable and compliant with medications prescribed by their primary care provider. A review of prescribed drugs should be undertaken in order to recognize any medications that may interfere with or impact upon the success of fertility treatments. This includes the use of androgens which are known to dramatically lower sperm counts and