The inner vaginal lining consists of hormone-sensitive, nonkeratinized squamous epithelium. The vaginal microbiota (VMB) serves to protect women of childbearing age from infections. It is composed of aerobic, facultative anaerobic, and obligate anaerobic bacteria, with anaerobes outnumbering aerobes by 10 : 1. Bacterial populations may vary depending on the vaginal microenvironment and the patient’s overall health.

Composition of normal VMB: Lactobacillus spp., Staphylococcus aureus, Staphylococcus epidermidis, group B Streptococcus, Enterococcus faecalis, Staphylococcus spp., diphtheroids. Aerobic bacteria: Escherichia coli, Enterobacterales spp., Citrobacter spp., Klebsiella spp., Proteus spp., Acinetobacter spp., Pseudomonas sp. Anaerobic gram-positive cocci: Peptostreptococcus spp., Clostridium spp. Anaerobic gram-positive bacilli: Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Аctinomyces israelii, Eubacteria spp. Gram-negative anaerobes: Fusobacterium spp., Prevotella spp., Veillonella, and Candida albicans. Alterations in the VMB may trigger nonspecific inflammation of the vaginal mucosa.

Bacterial Vaginosis

Bacterial vaginosis develops due to an unbalanced VMB. The VMB composition regulates vaginal pH. When the VMB’s acidity is compromised, lactobacteria cease to dominate, and the vaginal pH increases, leading to excessive growth of pathogens, such as Gardnerella vaginalis, Mobiluncus spp., Prevotella spp., Prophyromonas spp., Peptostreptococcus spp., Mycoplasma hominis, Ureaplasma spp., etc.

Complaints

Patients may report abnormal, profuse vaginal discharge that is yellowish-green or gray in color and has a foul-smelling, “fishy” odor.

Gynecological Speculum Examination

The vaginal mucosa typically appears normal. However, large amounts of gray and yellowish-green discharge are observed.

The Amsel criteria are used to diagnose the condition. They include four signs:

1. Profuse vaginal discharge;
2. Vaginal pH over 4.5;
3. Positive amine test;
4. Presence of clue cells revealed upon microscopic examination.

The diagnosis is established based on the presence of three out of four criteria.

Nonspecific Vaginitis

Nonspecific vaginitis is an inflammation of the vaginal mucosa induced by an opportunistic pathogenic VMB. Escherichia coli is its main driver, typically associated with poor or incorrect hygiene. Hypoestrogenism is often associated with a streptococcus-induced vaginitis.

Irrespective of the etiology, patient’s complaints and clinical manifestations of nonspecific vaginitis are similar.

Clinical Manifestations

The condition is characterized by profuse gray or yellow vaginal discharge, dyspareunia (painful sexual intercourse), and dysuria (painful or uncomfortable urination). Vaginal itching and erythema may be observed, whereas burning sensations, pain, or vaginal bleeding are rare. A gynecological speculum examination reveals a hyperemic vaginal mucosa.

Diagnosis

1. Microscopic examination of a vaginal smear: A ×10 microscopic exam helps assess epithelial cell types (mature, parabasal, basal, or clue cells) and identify any yeasts or pseudohyphae. Microorganism and cell count in the field of view is generally performed at ×40 magnification.
   • In women of childbearing age, the VMB should be dominated by Lactobacillus spp., which appear as large rods.
   • Trichomonas vaginalis is a flagellated protozoan that is slightly larger than a leukocyte.
   • Yeast cells and erythrocytes are similar in size.
   • Pseudohyphae are represented by chains of cells formed by budding.
2. KOH treatment: An isolated vaginal discharge sample is treated with a 10 % KOH solution. If the number of anaerobic bacteria (Gardnerella vaginalis, Mobiluncus spp., etc.) is increased, amines are typically formed. When treated with KOH, amines evaporate and produce a fishy odor.
3. DNA-testing: This technique is considered a highly sensitive diagnostic method. It helps identify Gardnerella vaginalis, Candida spp., Trichomonas vaginalis, Сhlamydia spp., Neisseria gonorrhoeae, as well as G. vaginalis, Prevotella spp., Mobiluncus spp., G. vaginalis, A. vaginae, Escherichia coli, Streptococcus spp., Staphylococcus spp., etc. Lactobacillus spp. (L. crispatus, L. jensenii, and L. gasseri) may also be detected.
4. pH-testing: The test is performed using a testing strip that is inserted directly into the vagina along its lateral wall. Falsely elevated results may be due to cervical discharge, sperm, or blood.
5. Microscopic examination of a vaginal smear with Gram staining according to the Nugent criteria.
6. Cell culture: This method has limited value in assessing vaginitis.

Treatment

Symptomatic vaginitis requires medical treatment. Treatment regimens:

• Metronidazole, 500 mg, orally;
• Metronidazole vaginal gel, 0.75 %, one applicator;
• Clindamycin vaginal cream, 2 %, one applicator;
• Clindamycin vaginal suppositories, 100 mg.

Pregnancy

All symptomatic pregnant women should undergo treatment. The main consideration in such instances is the risk of unfavorable pregnancy outcomes, including premature rupture of the membranes, premature birth, intraamniotic infection (chorioamnionitis), and postpartum endometritis. Oral metronidazole has proven most effective in this case, with no significant difference between oral and intravaginal formulations. Recent studies in pregnant women have also shown a high safety and efficacy profile of clindamicine.

Atrophic Vaginitis

Atrophic vaginitis is one of the manifestations of genitourinary syndrome of menopause (GSM). This condition involves a combination of signs and symptoms caused by decreasing sex steroids. Eventually, it leads to atrophic alterations of the labia, clitoris, vestibule of the vagina, vagina, urethra, and urinary bladder.

Etiology and Pathogenesis

Decreased sex steroids, estrogen in particular, trigger atrophic alterations in the vaginal mucosa and reduce glycogen deposition in the vaginal epithelium. This substance is metabolized by local bacterial communities to produce organic acids that protect the genital tract. As a result, Lactobacillus spp. concentration drops and pH increases. This promotes the growth of pathogenic bacteria, leading to vaginitis.

Androgens (i.e., dehydroepiandrosterone, androstenedione, and testosterone) are major estrogen precursors. In healthy premenopausal women, androgens are produced in much higher quantities than estrogens. As androgen receptors are abundant in the urogenital tract, androgen-dependent protein-containing products exert trophic effects on the tissues of the urogenital organs (the vestibule of the vagina, clitoris, urethra, vagina, urinary bladder, muscles/tendons of the pelvic floor). Apart from estrogens that are no longer produced after the menopause, an age-related decrease in androgens may also cause GSM signs and symptoms.

Clinical Manifestations

Patients are concerned about:

• Dryness of their genitalia, burning sensations, and irritation;
• Symptoms during sexual intercourse, such as absence of discharge, decreased lubrication, discomfort, dyspareunia, or vaginal bleeding associated with sexual intercourse;
• Signs of bladder disturbances, dysuria, and relapsing urinary tract infections. Note that these symptoms in postmenopausal women tend to adversely affect their sexual interest, intimacy, and relations with their partner, as well as mood and self-esteem.

Diagnosis

Upon speculum examination, the vaginal mucosa appears thin and flat; no discharge is observed, and local petechiae or ulcerations may develop.

Treatment

Intravaginal therapy is a first-line medical option recommended by the International Menopause Society (IMH). Women should start their therapy with the lowest dose and frequency to manage their symptoms effectively.

Intravaginal therapy

Intravaginal estrogen is only suitable for women who present with vaginal symptoms. This type of therapy is less potent than a systemic regimen. Generally, progestogen is not used intravaginally. Endometrium follow-up is not necessary if there is no postmenopausal bleeding that requires evaluation. Intravaginal therapy aims to increase estrogen levels in the vaginal epithelium and uroepithelium. It also helps postpone atrophic alterations with minimal systemic effects. A Cochrane review included women who reported symptom improvement and did not reveal any differences between the following pairs of formulations: estrogen ring and estrogen cream, estrogen ring and estrogen pills, estrogen pills and estrogen cream.

Systemic therapy

Estrogen alone is generally used in women who have undergone a total hysterectomy, whereas estrogen in combination with progestagen is preferred in women with an intact uterus.

Synthetic equivalent to endogenous dehydroepiandrosterone (DHEA)

A synthetic equivalent to endogenous dehydroepiandrosterone (DHEA) is approved for moderate and severe dyspareunia. The medication should be administered intravaginally once daily (QD). The therapy has been associated with a significant improvement in vaginal pH and symptoms. However, serum estradiol and testosterone levels remain unaffected. Upon visual examination, vaginal discharge and color, thickness, and integrity of the epithelium also improve. Endometrial safety of the intravaginal formulation has been demonstrated in relevant short- and long-term studies. Abnormal vaginal discharge and Pap test deviations are among the most common side effects.

Oral selective estrogen receptor modulator (SERM)

Oral selective estrogen receptor modulator (SERM) is approved for dyspareunia and vaginal dryness. Nonclinical studies have shown that this medicine may have a favorable estrogenic effect on bones and an antiestrogenic effect on mammary gland tissues. However, it is not authorized for osteoporosis prevention or breast cancer treatment. A meta-analysis of randomized study data has revealed that SERMs are well tolerated and have a favorable safety profile.

Estriol

Estriol is a naturally occurring estrogen. A low dose of intravaginal estriol gel (0.005 %) has been shown to significantly increase the vaginal cell maturation index and reduce vaginal pH compared to a postmenopausal control group.

Symptomatic treatment

1. Lubricants: Women reluctant to use intravaginal estrogen may opt for nonhormonal lubricating and moisturizing treatments. This therapy aims to relieve vaginal dryness and dyspareunia for a short period. Water-, silicone-, mineral-, or plant-based lubricants should be applied to the vagina and vulva before sexual intercourse.
2. Hyaluronic acid: Intravaginal hyaluronic acid is available as a colorless gel. It contains a hyaluronic acid derivative that releases water molecules into the tissue. This prevents vaginal dryness and does not irritate the vaginal mucosa.
3. Physiotherapy/dilators: Women with atrophic vaginitis and vaginismus may try a mild dilation technique with moisturized dilators of various sizes. Special exercises that help train and relax pelvic floor muscles are also recommended.
4. Laser treatment: This is a method that utilizes a CO2 fractional laser or erbium:YAG laser. Several small-scale studies have demonstrated that CO2 fractional laser therapy may restore the vaginal epithelium to its premenopausal state and increase the number of lactobacteria. However, leading experts do not approve of this method and warn against it to treat GSM, as there are no well-controlled long-term studies to prove its safety and efficacy.

Candidal Vaginitis

Candidal vaginitis is an inflammation of the vaginal mucosa. It is typically associated with Candida albicans but may be triggered by other Candida species or yeasts. It is estimated that during their lifetime, 75 % of women have at least one case of сandidal vaginitis, and 40–45 % experience two or more episodes. Around 10–20 % of women develop a complicated form that necessitates special diagnostic and therapeutic measures.

Clinical Manifestations

Patients complain of pruritus, pain, vaginal mucosa edema and hyperemia, as well as dense, profuse vaginal discharge. Vulvar edema, fissures, excoriations, and dysuria may be observed. Candidal vaginitis may be classified as uncomplicated and complicated based on its clinical manifestations, microbiological testing, the patient’s general health, and response to treatment.

Clinical criteria for uncomplicated candidal vaginitis:

• Sporadic or rare episodes;
• Mild symptoms;
• Most likely associated with Candida albicans;
• Observed in women who do not receive immunosuppression therapy.

Clinical criteria for complicated candidal vaginitis:

• Recurrent candidosis;
• Severe symptoms;
• Not associated with Candida albicans;
• Women with diabetes mellitus, immunodeficiency disorders (e.g., HIV), concomitant immunodeficiency, or those receiving immunosuppression therapy (e.g., corticosteroids).

Recurrent candidal vaginitis is diagnosed if three or more episodes of symptomatic disease are reported within one year. It may have an idiopathic form or develop as a secondary condition (associated with frequent use of antibiotics, diabetes mellitus, etc.). Its pathogenesis is not yet clear, as the majority of women do not have any predisposing or underlying conditions. Candida glabrata and other non-albicans Candida species are observed in 10–20 % of women with recurrent candidal vaginitis.

Diagnosis

A women may be diagnosed with candidal vaginitis if she has signs and symptoms of vaginitis. Moreover, microscopy should reveal budding, hyphae, and pseudohyphae. Candida glabrata does not form hyphae and pseudohyphae, which complicates the diagnosis. Candidal vaginitis does not affect vaginal pH (< 4.5). Wet preparations treated with 10 % KOH provide better visualization of yeasts and mycelium, as it destroys cell bulk that may conceal the causative agent. A symptomatic condition and negative microscopy may necessitate a culture test for vaginal Candida spp. If bacterial culture is not feasible, empirical treatment may be an option. An asymptomatic disease with positive culture does not require treatment, as Candida spp. and yeasts are a normal part of the VMB in 10–20 % of women.

Differential Diagnosis

A thorough investigation and relevant testing play a crucial role in identifying other causes of vaginal symptoms, including sexually transmitted infections (STIs), malignant tumors of the vulva, vagina, and cervix; inflammation of the pelvis, vulvovaginal herpes, vaginal fistulas, trauma, or vulvovaginal dermotosis.

Treatment

Uncomplicated candidal vaginitis may be effectively treated with short-term local medicines (i.e., single-dose or short-term regimens for 1–3 days). Azole antifungal agents relieve symptoms in 80–90 % of patients who complete their treatment course.

• Clotrimazole vaginal gel, 1 %, 5 g;
• Clotrimazole vaginal gel, 2 %, 5 g;
• Miconazole vaginal gel, 2 %, 5 g;
• Miconazole vaginal gel, 4 %, 5 g;
• Miconazole vaginal suppository, 100 mg;
• Miconazole vaginal suppository, 200 mg;
• Miconazole vaginal suppository, 1200 mg;
• Tioconazole vaginal ointment, 6.5 %, 5 g;
• Butoconazole vaginal cream, 2 %, 5 g (single-dose bioadhesive);
• Terconazole vaginal gel, 0.4 %, 5 g;
• Terconazole vaginal gel, 0.8 %, 5 g;
• Terconazole vaginal suppository, 80 mg.

Tablet formulation

• Fluconazole, 150 mg, orally.

Vaginitis associated with non-albicans Candida species

So far, an optimal treatment option for this type of vaginitis has not been devised. However, fluconazole and azole therapy (either oral or local) has been proven more efficient when used for longer periods (7–14 days). In cases of relapse, boric acid (capsule, 600 mg) is indicated for vaginal use. This treatment regimen eradicates infection in 70 % of cases.

Recurrent vulvovaginal candidosis

Most cases of recurrent vulvovaginal candidosis are associated with Candida albicans and respond well to short-term oral or local azole therapy. To maintain the effect, initial local therapy should be longer (7–14 days) or include a single oral dose of fluconazole (100 mg, 150 mg, or 200 mg).

Oral fluconazole therapy (100 mg, 150 mg, or 200 mg) once a week for 6 months helps maintain remission. If not feasible, periodic local therapy may be considered.

Pregnancy

Pregnant women should receive only local azole therapy for 7 days.

Genital Herpes

Genital herpes is a chronic, life-long viral infection. This disease may be caused by two types of herpes simplex virus (HSV) — HSV-1 and HSV-2. Most cases of recurrent genital herpes are triggered by HSV-2. Note that many HSV-2 patients do not present with any clinical manifestations. This means that genital herpes may be transmitted by those who are unaware of their condition.

Clinical Manifestations

Upon gynecological speculum examination, herpetic vaginitis may be suspected based on vaginal mucus edema, tender vesicular rash, or ulcerative lesions. The process is typically self-limited. During an interview, a patient may mention symptoms indicative of neurological complications. Nonspecific symptoms, such as fever, lymph node enlargement, and fatigue, may also be observed. However, the disease may be absolutely asymptomatic. Recurrent and asymptomatic conditions are more common in cases of HSV-2 infection. Bear in mind that patients with vaginitis associated with HSV-2 are 2–3 times more likely to be infected with HIV. Therefore, all genital herpes patients should also be referred for HIV testing.

Diagnosis

Upon examination, the diagnosis is complicated by the absence of typical self-limited, recurrent, tender, vesicular, or ulcerative lesions associated with HSV. When the genitalia are affected, the clinical diagnosis of genital herpes should be confirmed by virology testing for a specific HSV type. Otherwise, specific HSV serology tests may be utilized. Cytological detection of cellular changes induced by HSV infection is considered a nonsensitive and nonspecific method to diagnose genital conditions. A direct immunofluorescent assay utilizing fluorescein-conjugated monoclonal antibodies (mAb) helps identify HSV antigen in samples; however, it is not sensitive enough and therefore not recommended.

Treatment

First clinical episode of herpetic vaginitis: All patients with the first episode of herpetic vaginitis should receive antiviral therapy.

Recommended regimens:

• Acyclovir, 400 mg, orally;
• Famciclovir, 250 mg, orally;
• Valacyclovir, 1 g, orally;
• Acyclovir, 200 mg, orally.

If no treatment effect has been achieved, the therapy may be extended up to 10 days.

Recurrent herpetic vaginitis: Antiviral therapy may be suppressive to control relapses or occasional to reduce or limit the duration of lesions.

Occasional therapy for recurrent herpetic vaginitis induced by HSV-2:

Occasional therapy for recurrent herpetic vaginitis is most effective if started within 1 day after rash onset or during a prodrome that precedes a rash.

Recommended treatments:

• Acyclovir, 800 mg, orally.
• Famciclovir, 1 g, orally;
• Famciclovir, 500 mg, then 250 mg;
• Famciclovir, 125 mg;
• Valacyclovir, 500 mg, orally;
• Valacyclovir, 1 g, orally.
• Acyclovir, 400 mg, orally is also effective but not recommended due to its dosage regimen.

Suppressive therapy for recurrent herpetic vaginitis induced by HSV-2:

Suppressive therapy reduces recurrence rates of herpetic vaginitis by 70–80 % in patients with frequent disease episodes (more than six per year). Patients who receive this type of therapy report no symptoms. Long-term safety and efficacy have been well-documented in patients who receive acyclovir, valacyclovir, and famciclovir daily. Many patients with frequent relapses who receive suppressive therapy report an improved quality of life compared to those receiving occasional therapy.

Recommended regimens:

• Acyclovir, 400 mg, orally.
• Valacyclovir, 500 mg, orally;
• Valacyclovir, 1 g, orally;
• Famciclovir, 250 mg, orally.
• In patients with frequent relapses (i.e., ≥ 10 episodes per year), valacyclovir, 500 mg, once daily (QD) may be more effective than other valacyclovir or acyclovir dosing regimens.

Recurrent herpetic vaginitis induced by HSV-1:

Unlike HSV-2, herpetic vaginitis induced by HSV-1 is associated with fewer relapses after the first episode. There are currently no data to prove that suppressive therapy can effectively prevent HSV-1 transmission.

Prevention: If used consistently and correctly, male latex condoms have been proven to effectively reduce the risk of genital herpes transmission. However, the odds are never zero. In patients who present with serological signs of HSV-2 (including combination testing if needed) but have no other symptoms, neither occasional, nor suppressive therapy is recommended to prevent relapses.

Pregnancy

All pregnant women should be interviewed to determine whether they have genital herpes or other genital symptoms associated with HSV infection. Prodromal symptoms, such as pain or burning sensations in the affected area prior to vesicles, must be determined. To deliver via vaginal birth, all women should be referred for a thorough checkup for herpetic rash. Women with recurrent genital herpes must undergo cesarean section to reduce the risk of neonatal HSV infection; however, the odds of transmitting the disease to a newborn still exist. The following suppressive treatments are recommended for this group of pregnant women:

• Acyclovir, 400 mg, orally;
• Valacyclovir, 500 mg, orally.

The treatment should commence from week 36 of pregnancy. There is no evidence to prove that antiviral therapy is effective in HSV-seropositive asymptomatic women with no prior herpetic infection.

Tuberculous Vaginitis

Genital tuberculosis is the second most common form of tuberculosis after pulmonary tuberculosis. The disease tends to affect the female genitalia in 1.5–2 % of cases.

Tuberculous vaginitis is a specific inflammation of the vagina caused by Mycobacterium tuberculosis. Genital tuberculosis typically develops as a hematogenous infection; in rare instances, it may spread through lymph.

Complaints: Patients may be concerned about nagging lower abdominal pain, pathological vaginal discharge, vaginal bleeding, or infertility.

Clinical Manifestations

A gynecological speculum examination may reveal a superficial tuberculosis-induced vaginal ulcer with undermined edges. The ulcer bed is infiltrated, and the base is covered with a yellowish or reddish-gray scale. Off-white miliary tubercles may be observed along the ulcer edges that turn pale when pressed with a spatula. An additional rectal examination is essential to rule out any rectovaginal fistulas.

Note that tubercular ulcers are a long-term condition.

Patients may report general symptoms, such as low-grade fever, weakness, decreased energy, fatigue, poor appetite and sleep, night sweats, weight loss, and skin dryness.

Diagnosis

Microscopic and cytological examination help identify specific tuberculous inflammation in the samples. A bacteriological or culture test for Mycobacterium tuberculosis may utilize vaginal discharge, discharge from the ulcer, menstrual blood, or an aspirate as samples. However, genital tuberculosis may produce negative bacterial test results, even if the diagnosis has been confirmed microscopically. A nucleic acid amplification test (NAAT) allows for a rapid identification of Mycobacterium tuberculosis in samples. Xpert MTB/RIF is a NAAT that helps to both determine and identify the Mycobacterium tuberculosis complex. It is also useful in finding any genetic mutations that may indicate rifampicin resistance, one of the most effective tuberculosis medicines. A tuberculin skin test or interferon-gamma release assay (IGRA) is also an option.

Treatment

Medical therapy should be administered by healthcare professionals in specialized hospital units. It typically combines two to three of the following medications:

• Isoniazid;
• Rifampin;
• Rifabutin;
• Rifapentine;
• Pyrazinamide;
• Ethambutol.

In case of resistance or additional complications, other medications may also be considered. Surgical therapy may be performed as needed.

Syphilitic Vaginitis

Syphilis is a systemic disease in humans that is caused by Treponema pallidum. Syphilitic vaginitis is a manifestation of early primary genital syphilis.

Incubation period: It typically takes 10–90 days from the moment of infection to develop a syphilitic chancre.

Clinical Manifestations

Upon a gynecological speculum examination, a single superficial chancre is typically painless; the bed and discharge are clear. A chancre may be accompanied by regional lymphadenopathy. Multiple, painful, and deep chancres are atypical lesions that resemble herpetic ulcers. As a matter of precaution, any anogenital ulcer should be treated as a syphilitic one until proven otherwise.

Diagnosis

Dark-field microscopy and molecular profiling for Treponema pallidum using effusion or tissue samples are the ultimate methods to diagnose early syphilis. If syphilis is suspected, two serological tests are required: nontreponemal (i.e., VDRL or RPR, RST, USR, TRUST rapid tests) and treponemal tests (i.e., ELISA, immunoblotting, CLIA, PCT, IHA, immunofluorescence test, TPI). Diagnosis should be based on tests of both types (treponemal and nontreponemal). Otherwise, primary syphilis patients may have false-negative results, whereas healthy patients or patients with syphilis in the past may get false-positive results.

The immunohistochemistry (IHC) analysis using a polyclonal antibody against Treponema pallidum may be effective in identifying treponemas in skin, conjunctive, or tissue samples, but it is not suitable for routine diagnosis.

Treatment

Parenteral penicillin G is preferred for treatment at all syphilis stages. The exact medication, its strength, and treatment duration depend on the disease stage and clinical manifestations. Eventually, blood serum should demonstrate treponemocidal concentrations of antimicrobial agents. For penicillin, this level is > 0.018 mg/L, which is much less than the maximal effective concentration in vitro (0.36 mg/L) and should be maintained for at least 7–10 days. Longer therapy may be needed as the disease progresses. Clinically, later stages of syphilis treated with short-term regimens have shown more relapses.

This phenomenon may be explained by a slower treponema division in late syphilis.

An allergic reaction to penicillin may require alternative approaches:

• Desensitization to penicillin followed by first-line therapy;
• Other medications, such as ceftriaxone or oral doxycycline.

Tests to monitor treatment effects

VDRL or RPR quantitative assays are widely used to control disease progression and treatment effects during follow-up visits. An antibody titer should be determined on the first treatment day, serving as the baseline antibody level to compare with subsequent assays. Blood serum should be taken 1 month, 3 months later, and then every 6 months. The same laboratory, utilizing a single technique, should perform all the tests. The tests should be conducted until the results are negative or reach a low plateau (1:1–1:4 during 1 year, provided there is no continuous risk). Patients who have persistent high titers should be followed closely.

Pregnancy

Pregnant women with early syphilis and untreated early syphilis may transmit the infection to their newborns in 70–100 % of cases. Stillbirths may comprise up to one third of all pregnancy outcomes. A fetus is typically infected in the late preterm period (after week 28). If treated timely (before week 28), congenital abnormalities may be prevented. Parenteral penicillin G is the only treatment option that has been proven effective in pregnant women with syphilis.