Gynecology and
Obstetrics

PRENATAL OBSTETRICS

Change in fibroid volume across gestation

The effect of pregnancy on fibroid volume has been unclear because of the lack of prospective longitudinal data from a large diverse obstetric population. To address this gap, a prospective cohort study performed six obstetric ultrasounds at timed intervals between 10 and 41 weeks of gestation in nearly 2800 patients at 12 clinical sites in the United States [1]. Change in total fibroid volume was affected by initial volume: increasing by 2 percent per week in patients with initially small volumes (diameter ≤1 cm), no or minimal change in those with initially medium volumes (diameter 1 to <3 cm), and decreasing by 2 percent per week in those with initially large volumes (diameter ≥3 cm). Change in volume was also affected by maternal age, race/ethnicity, parity, and miscarriage history. These findings will be useful in counseling patients with fibroids about what to expect during pregnancy.

Lack of efficacy of vaginal progesterone in patients with prior spontaneous preterm birth

In 2021, the American College of Obstetricians and Gynecologists endorsed offering either vaginal progesterone or intramuscular hydroxyprogesterone caproate supplementation to patients with a singleton pregnancy and a prior spontaneous preterm birth (sPTB) to reduce the risk of recurrence. However, a 2022 meta-analysis limited to trials assessing use of vaginal progesterone for preventing recurrent sPTB in this population found that reductions in sPTB were not statistically significant after restriction to trials at low risk of bias and adjustment for small-study effects [2]. We offer hydroxyprogesterone caproate to patients with a singleton pregnancy and history of sPTB and offer vaginal progesterone to patients with a short cervix in the current pregnancy. However, the efficacy of any progesterone supplement for prevention of sPTB remains controversial.

Prenatal cell-free screening results and maternal malignancy

In pregnant patients with a malignancy, noninvasive fetal aneuploidy screening with cell-free DNA (cfDNA) may detect circulating cfDNA from the tumor in addition to the usual placental and maternal cfDNA. In a study including over 168,000 pregnant patients who underwent prenatal genome-wide cfDNA screening, malignancy-suspicious results (ie, multiple chromosome imbalances) led to a new diagnosis of malignancy in 16 patients [3]. The appropriate clinical evaluation of malignancy-suspicious prenatal cfDNA results is unclear, in part because the results have no correlation with the tissue of origin of the malignancy. Patients undergoing prenatal fetal aneuploidy screening with a cfDNA test should be aware of the possibility of this rare incidental finding.

Interpregnancy interval and adverse pregnancy outcomes

A short or long interpregnancy interval appears to increase the risk for some adverse pregnancy outcomes, but it is challenging to analyze because of multiple confounding variables. A recent study including over 700,000 consecutive first- and second-live born sibling pairs was able to control for several such variables since 99% of the mothers were of Han Chinese ethnicity and <35 years of age and a matched-sibling analysis accounted for adverse outcomes of the first sibling [4]. This study confirmed previous data that short (<6 months) or longer (≥36 months) interpregnancy intervals are associated with greater odds of adverse birth outcomes, such as preterm birth and low birth weight, compared with an 18- to 23-month interval. We recommend that most patients should strive for an interpregnancy interval of 18 to 24 months.

Use of exome sequencing in euploid anomalous fetuses

Exome sequencing (ES) is increasingly used for prenatal genetic diagnosis of euploid fetuses with structural anomalies, but questions remain about the best use of the technique. In a meta-analysis of the diagnostic yield of ES in this clinical setting (72 reports, over 4300 fetuses), the pooled incremental diagnostic yield was 31 percent and higher for cases in which a multidisciplinary team with expertise in genetics suspected a monogenic etiology compared with unselected cases (42 versus 15 percent) [5]. Incremental diagnostic yield also varied among phenotypic subgroups, ranging from 2 percent for isolated enlarged nuchal translucency to 53 percent for isolated skeletal abnormalities. These findings support our opinion that the decision to use ES should be made in consultation with a clinician specializing in genetic testing.

Azithromycin instead of erythromycin for prophylaxis in preterm prelabor rupture of membranes

In patients with preterm prelabor rupture of membranes (PPROM), a commonly used regimen for infection prophylaxis is ampicillin plus erythromycin intravenously (IV) for 48 hours, followed by amoxicillin plus erythromycin orally for 5 days. However, a new meta-analysis of five observational studies comparing use of mostly a single dose of IV azithromycin versus multiple days of erythromycin as part of prophylaxis in nearly 1300 pregnancies with PPROM found that azithromycin was associated with a lower rate of clinical chorioamnionitis (14 versus 24 percent) [6]. For the macrolide part of the regimen, our approach of giving a single dose of azithromycin in lieu of a multiple-day course of erythromycin is supported by these findings and has the advantages of ease of administration, improved gastrointestinal tolerance, favorable cost profile, and similar or better efficacy.

Respiratory syncytial virus immunization in pregnancy

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality in infants and theoretically may be prevented with maternal immunization; however, such a vaccine is not yet available. In an interim analysis of a phase 2b randomized trial evaluating the safety and efficacy of RSV immunization in over 400 pregnant patients in their second or third trimester, infants of vaccinated mothers had a lower rate of RSV-associated medical illness (0.7 versus 4.9 percent) and a nonstatistically significant reduction in severe RSV-associated illness compared with infants of unvaccinated mothers [7]. Serious adverse events in pregnant patients and infants were similar for the vaccinated and unvaccinated groups. These findings are promising and need to be confirmed.

GYNECOLOGY

Low-dose vaginal estrogen is an effective treatment for moderate to severe symptoms of genitourinary syndrome of menopause (GSM) unresponsive to nonhormonal management (vaginal moisturizers, lubricants), but its safety in patients with breast cancer is unclear. In a study of postmenopausal patients with a history of early estrogen-positive breast cancer treated with aromatase inhibitors (AI), those who used vaginal estrogen after the breast cancer diagnosis had a higher risk of breast cancer recurrence compared with nonusers (adjusted hazard ratio 1.39, 95% CI 1.04-1.85) [20]. This association was not seen in patients treated with tamoxifen. While there are several limitations to this study, these data support our general practice of prescribing vaginal estrogen for management of GSM in patients with breast cancer treated with tamoxifen but not those treated with AI.

Treatment of recurrent vulvovaginal candidiasis

Patients with recurrent vulvovaginal candidiasis (RVVC, defined as ≥3 culture-confirmed episodes in ≤12 months) who do not respond to oral fluconazole therapy have had few other treatment options. In an industry-sponsored trial comparing treatment and maintenance with either oteseconazole (a novel azole) or fluconazole/placebo in 185 females with active RVVC, fewer patients receiving oteseconazole experienced ≥1 culture-confirmed candidiasis episodes during the 48-week maintenance phase compared with fluconazole/placebo (5 versus 42 percent, respectively) [21]. Where available, oteseconazole is a therapeutic option for patients with culture-confirmed RVVC who do not respond to fluconazole therapy and who are not pregnant, attempting pregnancy, or lactating.

Levonorgestrel dose for emergency contraception in individuals with obesity

Because levonorgestrel (LNG) emergency contraception (EC) appears to be less effective in individuals with obesity, doubling the LNG EC dose has been proposed to improve efficacy in this population. However, in a randomized pharmacodynamic trial comparing usual (1.5 mg) versus double-dose (3 mg) LNG EC in 70 individuals with obesity and a dominant follicle ≥15 mm on ultrasound, the proportion of individuals that achieved at least five days with no evidence of rupture was not significantly different between groups, and the time to follicle rupture was also similar for both groups [22]. As there was no clear reduction or delay in ovulation, we use the 1.5 mg LNG EC dose for all individuals but counsel those with obesity that other options (eg, copper intrauterine device) are more effective.

Vaginal laser therapy for treatment of stress urinary incontinence

Efficacy of vaginal laser therapy for treatment of female urinary incontinence has been debated because supporting data are from small observational studies. In a prospective, sham-controlled trial including 101 females ages 18 to 80 years with stress urinary incontinence (SUI), subjective and objective SUI rates were similar between the sham and active groups three months after therapy (subjective SUI: 96 versus 98 percent and objective SUI: 80 percent for both groups) [23]. UpToDate continues to advise against vaginal laser therapy for routine treatment of female SUI as there is insufficient evidence to support its use.

Outcomes of no-test abortion

No-test abortion (also referred to as history-based abortion) for pregnancies up to 77 days is increasing; however, studies evaluating outcomes and safety are limited. In a multicenter, retrospective study including nearly 2400 patients undergoing history-based abortion that had abortion outcome data, 95 percent had a complete abortion without additional intervention; the remainder either required an additional procedure, such as uterine aspiration, additional medication, treatment for ectopic pregnancy, or had a continuing pregnancy [24]. Abortion-related adverse events (hospital admission, major surgery, transfusion) were rare. These data are consistent with previously published outcomes on clinic-based medication abortion and useful for counseling patients seeking medication abortion.

GYNECOLOGIC SURGERY

Hysteroscopic metroplasty and pregnancy outcomes

Hysteroscopic metroplasty may be performed in patients with a uterine septum to decrease the risk of adverse pregnancy outcome, but the efficacy is unclear. In a meta-analysis (one randomized trial, 10 cohort studies) comparing hysteroscopic resection with expectant management in nearly 1600 patients with a complete or partial uterine septum, surgery was associated with reduced risks of miscarriage and malpresentation, but not with significant changes in clinical pregnancy, term live birth, and cesarean birth rates [27]. In our practice, we counsel patients with a uterine septum that metroplasty may improve some pregnancy outcomes in specific settings (eg, recurrent pregnancy loss, primary infertility after exclusion of other causes).

Opportunistic salpingectomy and ovarian cancer risk reduction

Patients at average risk for epithelial ovarian, fallopian tube, and peritoneal carcinomas (EOC) may undergo opportunistic salpingectomy (OS) when undergoing hysterectomy or instead of tubal ligation, but the efficacy for reducing future EOC is unclear. In a large cohort study comparing patients undergoing OS with those undergoing hysterectomy or tubal ligation alone, OS was associated with fewer serous (0 versus 15) and epithelial (≤5 versus 21) ovarian carcinomas at up to nine years follow-up, as well as a reduction in the age-adjusted expected risk of these carcinomas [28]. When counseling patients undergoing hysterectomy or permanent contraception, we include the benefit of complete salpingectomy on EOC risk reduction.