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Management options

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Similar to the approach for HIV‐seropositive males, management of seropositive females requires careful multidisciplinary healthcare coordination [9]. First and foremost, the medical fitness of the woman should be verified in consultation with internal medicine and infectious disease specialists. Special attention to recent history of CD4 counts, viral load and general treatment compliance (including consistent condom use) is required. Psychosocial assessment is performed to screen for issues of substance abuse, mental health, domestic violence or other issues that are more prevalent in the HIV‐seropositive population and might affect reproductive fitness or compliance with care. Finally, consultation with maternal‐fetal medicine specialists or obstetricians specifically trained to manage HIV‐infected patients is indicated to discuss issues related to the antiretroviral therapy used during pregnancy, prenatal screening and diagnostic testing (specifically invasive diagnostic maneuvers, e.g. amniocentesis, that carry a risk of transmission), and the plan for delivery.

Once the patient’s medical and psychosocial fitness for pregnancy has been established, an HIV‐seropositive female with an HIV‐seronegative partner may be instructed in self‐insemination techniques synchronized with ovulation. For patients who object to self‐insemination, well timed intercourse that decreases the need for repetitive exposure is a reasonable alternative [10]. Recent studies have investigated the efficacy of pre‐exposure prophylaxis (PrEP) for the uninfected partner during the time conception is attempted to further safeguard the uninfected partner [11].

If unsuccessful after several attempts or if the patient is ≥ 35 years old or has a history suggestive of reproductive dysfunction (e.g. menstrual irregularity, poor antral follicle count), clinicians should initiate a basic infertility workup, including day 2–3 follicle stimulating hormone (FSH), semen analysis and hysterosalpingogram (aggressive antibiotic prophylaxis, e.g. doxycycline for 5–7 days or Azithromycin should be prescribed).

HIV‐seropositive females may be vulnerable to two major categories of infertility. First, HIV is known to coexist with a high prevalence of other sexually transmitted diseases, which may lead to pelvic inflammatory disease (PID) [12]. Tubal disease is therefore a common cause of infertility among HIV‐seropositive women [13,14]. Second, studies suggest that HIV may have a direct deleterious effect on the ovaries [15]. Various investigators have shown a higher rate of ovarian dysfunction [16,17], diminished ovarian reserve [18], premature ovarian insufficiency [19] and amenorrhea [20–22] in this population.

In population studies, HIV disease progression has been observed to be associated with a decline in fertility, even after controlling for nutritional status and weight loss [23], and with oligomenorrhea and amenorrhea [20]. However, it has been suggested that confounding variables, such as substance abuse and smoking, may have contributed to these disorders and more recent data from North America has not confirmed these findings [24]. One study evaluated ovarian reserve as reflected in anti‐Müllerian hormone (AMH) levels and found no association with HIV‐seropositivity [25].

If the couple demonstrates infertility, ART should be recommended. In the absence of significant male factor or tubal disease, intrauterine insemination (IUI) with or without controlled ovarian stimulation (COS) may also be recommended. IUI has been performed in HIV patients with good results [26], although it should be noted that because multiple pregnancy increases obstetric complications associated with higher rates of vertical transmission (e.g. preterm birth), aggressive COS is best avoided.

In the case of significant male factor, intra‐cytoplasmic sperm injection (ICSI) is the clear treatment of choice. Tubal disease can be addressed with IVF with or without ICSI; most practitioners nevertheless advocate using ICSI in order to minimize the amount of infected material in the laboratory by denuding the oocyte and performing repeated washings prior to fertilization [27]. In this regard, it should be noted that the American Society for Reproductive Medicine (ASRM) “highly recommends” that material from viral carriers be processed in a separate laboratory or designated space within the main laboratory using dedicated equipment [28]. Unfortunately, the heavy financial burden of fulfilling these recommendations has contributed to the scarcity of American centers offering treatment to HIV‐seropositive patients [10,29].

To date, there are no published cases of children born to HIV‐seropositive women after ART who were subsequently found to be HIV‐seropositive. Self‐insemination and IUI data in this setting are largely absent from the literature. However, many studies demonstrate overall poorer IVF outcomes in women with HIV compared with uninfected patients [26–27,30–32]. In two studies, an increased amount of gonadotropin and prolonged duration of stimulation were required in comparison to matched controls; however, this pattern was not consistently observed [27,33]. Overall, reported pregnancy rates are in the range of approximately 10–25%, slightly lower than those reported for age‐matched controls [27,31,34]. While it is possible these data may lend support to the negative effects of HIV on the ovaries, two factors should be considered:

1 In an effort to limit multiple pregnancy, fewer embryos were transferred in HIV‐seropositive patients; this may account for lower pregnancy rates. Indeed, implantation rates per embryo are generally more comparable to those of controls.

2 Other factors potentially associated with decreased ART success, including African race, leiomyomata and smoking are likely more prevalent in the HIV‐seropositive groups studied and these variables were not adequately controlled.

Ultimately, there is little doubt that for HIV‐seropositive women, who previously had few safe options for building a family, reproductive medicine and ART has had an enormously positive impact on their quality of life and disease prevention. Efforts need to continue to focus on making care more accessible and affordable in hope of expanding services universally.

Assisted Reproduction Techniques

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