The November issue of Contemporary OB/GYN is one you do not want to miss.

Volume 65 No 11: The Technology Issue, November 2020

COVID-19 during pregnancy may not cause adverse outcomes

The findings provide novel information on the outcome in pregnancy that are counter to smaller reports.

S2E8: Skeletal dysplasia with David Abel, MD

This episode of Pap Talk by Contemporary OB/GYN features David Abel, MD, as he discusses various elements of skeletal dysplasia and how practitioners can help their patients.

The ever-use of an intrauterine device (IUD) reduces the risk of ovarian cancer by an average of 30%, according to a rigorous meta-analysis in the Journal of Obstetrics and Gynaecology.

Vertigo risk factors in perimenopausal women

It has yet to be fully elucidated why postmenopausal women have a higher prevalence of benign paroxysmal positional vertigo (BPPV); however, the sudden decrease in estrogen during menopause can cause a rapid decrease in estrogen receptors, which may disturb otoconial metabolism and thus, increase the prevalence of BPPV.

Articles

It was a very busy week for the Contemporary OB/GYN team. 

In case you missed it: Nov. 30 to Dec. 4

“Whilst many studies focus on retrograde menstruation, and the formation and development of lesions in the pathogenesis of endometriosis, the mechanisms underlying the associated pain remain poorly described,” wrote the Australian authors.

Because endometriosis patients also have comorbidities like irritable bowel syndrome and overactive bladder syndrome, common nerve pathways innervating the colon, bladder and female reproductive tract can contribute to comorbidity via cross-organ sensitization.

Surgical removal of endometrial lesions can successfully alleviate pain, thus implicating these lesions in chronic pain; however, inconsistencies exist between pain severity and lesion score. Chronic pain also often returns within 12 months of lesion removal, despite the absence of lesion regeneration.

In fact, some reports indicate 20% to 28% of patients do not attain pain relief following surgery.

Growing evidence suggests that a chronic remodeling of the nervous system occurs in shared sensory neural pathways to induce a state of protracted peripheral and central sensitization and chronic pain in endometriosis patients.

More recent revelations of the mechanisms underlying the development of a chronic pain state in endometriosis point to cyclical bleeding from lesions and subsequent inflammation at lesion sites and in the peritoneal cavity. These proinflammatory responses result in sensory nerve activation and altered activation of nociceptive pathways.

An increase in extra-uterine debris during menstruation exacerbated by additional retrograde menstruation induces an enhanced inflammatory response within the peritoneum. This allows for the interaction of these immune cells with sensory nerves to induce chronic pelvic pain.

Long-term exposure to proinflammatory cytokines may activate and sensitize sensory nerves present in endometriotic lesions, thus initiating the transfer of pain to the central nervous system (CNS).

According to several studies, once endometrial fragments adhere to a peritoneal location and become lesions, they undergo a process of neoangiogenesis, whereby a new blood supply is created by generating new blood vessels to support growth and survival, along with synchronized innervation by nerve fibers (neurogenesis).

Studies have found that endometriosis-associated menstrual pain is greatest in women whose endometriotic lesions had increased nerve fiber innervation.

Adding to the pro-nociceptive environment induced by endometrial lesions in the peritoneal cavity, the accumulation of degraded tissue byproducts can directly sensitize sensory nerve fibers through receptors on nociceptive afferent nerves located within lesions. Sensitized sensory nerve fibers also maintain inflammation by a positive feedback loop known as neurogenic inflammation.

Chronic sensitization of peripheral sensory nerve fibers could induce sensitization of the CNS in endometriosis. Recent studies conclude that exposure to chronic stress early in life can increase the likelihood of chronic pelvic pain later in life, whereas episodes of acute stress can trigger or worsen symptoms.

This review offered evidence of an overall heterogeneity in endometriosis, as opposed to a “one size fits all” approach, indicating personalized treatment based on etiology and symptomatology.

“Shifting the paradigm of lesion-specific and cyclical inflammatory pain will continue to open up further areas to expand treatment opportunities,” wrote the authors.

The next step is to clarify disease-specific changes and their targets at the lesion, dorsal root ganglion (DRG), spinal cord, and brain levels.

Maddern J, Grundy L, Castro J, et al. Pain in endometriosis. Front Cell Neurosci. Published online October 6, 2020. doi:10.3389/fncel.2020.590823

Inflammation, neurogenic inflammation, neuroangiogenesis, peripheral sensitization and central sensitization all contribute to chronic pain in endometriosis, according to a review in the journal Frontiers in Cellular Neuroscience.

Mechanisms of endometriosis pain

The data below is a reflection of data collected weekly by the 

Centers for Disease Control and Prevention

 (CDC). The cases reported are only confirmed cases with laboratory evidence of SARS-CoV-2 infection.

Here’s the latest data, updated on December 3:

Pregnant women with COVID-19, United States:

Data is updated weekly based on data collected by the Centers for Disease Control and Prevention (CDC). The cases reported are only confirmed cases with laboratory evidence of SARS-CoV-2 infection. CDC’s case numbers are validated through a confirmation process with each jurisdiction.

Currently, there are 56 U.S.-affiliated jurisdictions reporting cases of COVID-19, including 50 states, District of Columbia, Guam, New York City, the Northern Marina Islands, Puerto Rico, and the U.S. Virgin Islands.

Find previous data and the latest COVID-19 updates 

Data on COVID-19 during pregnancy, as reported by the CDC, in collaboration with state, local, and territorial health departments and external partners.

COVID-19 Pregnancy Data in the United States: Dec. 3 update

Furthermore, most of the respondents noted that their oncologist had not formally asked them about such side effects.

“A patient and the sexual side effects she was experiencing inspired the development of the study,” said lead author James Taylor, MD, MPH, chief resident in radiation oncology at the Sidney Kimmel Cancer Center at Thomas Jefferson University in Philadelphia.

Survivorship care is a growing focus in oncology, due to improved outcomes and patients living longer after treatment. “Side effects that impact sexual function or desire are closely associated with quality of life, ranging from erectile dysfunction from prostate cancer treatment to vaginal dryness seen with endocrine therapy for breast cancer,” Taylor told 

The 2019 survey was conducted mostly online, through social media platforms Twitter and Facebook, representing patients treated at multiple clinics throughout the United States.

Of the 391 respondents eligible for analysis, 81% were female, and the three most common cancers were breast (67%), prostate (16%) and endometrial (6%).

Treatments included chemotherapy (78%), radiation therapy (54%) and hormone therapy (47%).

Overall, 87% of respondents reported some change after treatment that negatively impacted their sexual health and quality of life. The three most common sexual side effects were painful intercourse (73%), body image distortion (54%) and inability to achieve orgasm (42%).

In addition, fewer than half of respondents (47%) said they were counseled before treatment that their sexual health might be compromised by therapy.

Male cancer survivors were more than twice as likely than female cancer survivors to be asked and counseled about potential treatment sexual toxicity: 53% vs. 22% (P < 0.001).

Significantly more male patients also said they received a formal assessment tool like a survey: 32% vs. 5% of women patients (

“I was surprised by how common sexual toxicity is among survivors,” Taylor said. “I was also surprised by the gender disparity that we identified.”

A majority of respondents (51%) said they would be more comfortable if a discussion about sexual health was initiated by their provider and guided by a standard questionnaire on possible side effects.

“Patients seem to prefer completing a survey or questions about their sexual health in the clinic, then reviewing the information with their provider, rather than the physician directly asking the patient or the patient driving the discussion,” Taylor said.

A questionnaire given to all patients can reduce patient uneasiness and help bridge the discussion between patient and provider, according to Taylor.

“We need to incorporate counseling on sexual toxicity and side effects of cancer treatment into our clinics,” he said. “There are validated instruments that exist to help identify sexual toxicity in patients and we need to ensure they are being used.”

Taylor believes clinicians have the ability to solve the problem of sexual toxicity and help educate and inform patients on the sexual side effects of treatment.

Taylor and his colleagues are planning a follow-up study of providers and developing a quality improvement project to implement clinically.

Taylor reports no relevant financial disclosures.

The vast majority of cancer survivors reported that they experience sexual side effects after chemotherapy, radiation and other cancer treatments according to the results of a survey presented at the annual meeting of the American Society for Radiation Oncology.

Sexual health after cancer treatment

Likewise, hormone replacement therapy can reverse low otoconin 90 levels, thus reducing the incidence of BPPV.

These are two findings published in the journal 

 from a review of BPPV risk factors unique to perimenopausal women.

“Adoption of a customized approach considering the neurochemical changes in perimenopause will be extremely helpful for the management of BPPV in women,” wrote sole author Seon-Hae Jeong, MD, PhD, of the Department of Neurology at Chungnam National University Hospital and School of Medicine in Deajeon, South Korea.

Cooperative management among neurotologists, endocrinologists, and gynecologists is also important as a focus for neurotological disorders, including BPPV, in women.”

BPPV is the most common cause of recurrent vertigo, affecting more than 420 million adults worldwide and a lifetime prevalence of 10%. The disorder also increases with age, especially during menopause.

The review highlights the current state of knowledge about BPPV risk factors specific to women. Older age, head and neck trauma, inactivity, and ear problems are some of the common factors that may increase the susceptibility of women to BPPV.

Recurrent BPPV might also be caused by oral contraceptives because they may induce disturbances in the water and electrolyte balance, variances in endolymph pH, and abnormalities in carbohydrate or lipid metabolism. These occurrences could cause otoconial degeneration and subsequent otoconial detachment and BPPV.

In addition, some women are initially diagnosed with BPPV during pregnancy.

Decreased bone mineral density is also linked to the occurrence and/or recurrence of BPPV. In women undergoing rapid bone loss after menopause, bone resorption and urinary calcium ion excretion are increased; These changes are reversed by estrogen replacement therapy.

Because estrogen loss is a causal factor for bone loss during perimenopause, a specific estrogen replacement modulator could be used to treat postmenopausal BPPV patients.

One prospective study found that women taking postmenopausal hormone replacement therapy achieved better scores than the placebo group on the Kupperman scale for sweating, hot flashes, myalgia and vertigo.

“The hormonal fluctuation of ovarian neurosteroids might trigger the occurrence/recurrence of BPPV during the perimenopausal period,” Jeong wrote.

Another study concluded that the incidence of BPPV was significantly lower in patients taking estrogen for menopausal syndrome in two age groups: ages 45 to 65 and ages 65 and over.

A potential mechanism that allows for the efficacy of estrogen supplementation to decrease the occurrence of BPPV in women with menopause is estrogen blood levels that are more complete and more reliable, thus inducing protective effects, estrogen effects on autophagy and possible epigenetic modulation.

However, because the chronic use of hormone replacement therapy increases the risk of breast cancer, stroke and venous thrombosis, many postmenopausal women rely on alternative nonsteroidal estrogen mimetics or natural remedies.

Phytoestrogens, including soy isoflavones, could be an option, but so far there have been no reports on the efficacy of phytoestrogens on BPPV recurrence.

“Future studies are necessary to validate the effects of hormonal replacement therapy and phytoestrogen in women with recurrent BPPV,” Jeong wrote.

Jeong SH. Benign paroxysmal positional vertigo risk factors unique to perimenopausal women. Front Neurol. Published online October 16, 2020. doi:10.3389/fneur.2020.589605

Kim HJ, Lee JO, Choi JY, Kim JS. Etiologic distribution of dizziness and vertigo in a referral-based dizziness clinic in South Korea. J. Neurol. (2020) 267:2252–59. 10.1007/s00415-020-09831-2

Bech P, Munk-Jensen N, Obel EB, Ulrich LG, Eiken P, Nielsen SP. Combined versus sequential hormonal replacement therapy: a double-blind, placebo-controlled study on quality of life-related outcome measures. Psychother. Psychosom. (1998) 67:259–65. 10.1159/000012289

Liu DH, Kuo CH, Wang CT, Chiu CC, Chen TJ, Hwang DK, et al. . Age-related increases in benign paroxysmal positional vertigo are reversed in women taking estrogen replacement therapy: a population-based study in Taiwan. Front. Aging Neurosci. (2017) 9:404. 10.3389/fnagi.2017.00404

Postmenopausal women with elevated hypertension who participated in the high-intensity team sport of floorball, a form of indoor hockey, achieved a significant decrease in their blood pressure, according to a study from the Center for Team Sports and Health at the University of Copenhagen in Denmark.

The authors of the study, published in the 

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology,

 said that, although hypertension is associated with vascular dysfunction, it is unknown whether hypertensive postmenopausal women have blunted nitric oxide (NO)-mediated leg vasodilator responsiveness, and whether this is reversible by high-intensity training.

To bring clarity, the investigators examined the leg vascular conductance (LVC) in response to femoral-infusion of acetylcholine (ACh) and sodium nitroprusside (SNP), plus skeletal muscle markers of oxidative stress and NO bioavailability, before and after high-intensity training in postmenopausal women.

“We hypothesized that ACh- and SNP-induced LVC responsiveness was reduced in hypertensive compared to normotensive postmenopausal women and that 10 weeks of high-intensity training would reverse the blunted LVC response and decrease blood pressure,” wrote the authors.

The study evaluated nine postmenopausal women with high blood pressure and a control group of eight postmenopausal with normal blood pressure, all of whom had their last menstrual cycle at least 6 years before study enrollment.

All the women participated in twice-weekly floorball training for 10 weeks. Matches were played from 2 versus 2 to 5 versus 5.

Women with high blood pressure achieved a reduction in vascular stiffness that led to a decrease in blood pressure by 15 (systolic) and 9 (diastolic) mmHg, which corresponds to a 40% lower risk of death by heart attack and a 30% reduction for coronary artery disease.

However, because 4 of the 9 hypertensive women were on anti-hypertensive medication, vascular outcomes could be comprised. Nonetheless, when comparing the results of the medicated versus the non-medicated hypertensive women, no difference was observed in training-induced changes in leg vasodilator responsiveness.

The group of women with normal blood pressure had slightly elevated blood pressure at the beginning of the study, which is common among inactive postmenopausal women. But they too attained an impressive 10 mmHg decrease in systolic blood pressure.

Also, all study participants achieved on average a 10% reduction in visceral fat mass. Total fat mass also decreased by half a kilogram.

The authors noted the study results as particularly noteworthy because none of the women had previously played floorball and they were able to achieve excellent health results within a relatively short time.

The study also contradicts the notion that vascular smooth muscle in postmenopausal women cannot change with exercise. Vascular smooth muscle cell function was reduced by 30% to 40% in the women with high blood pressure compared to the control group.

After training, there was no difference in the vascular function between the two groups.

The study sheds light on the types of exercise that can effectively counteract the negative consequences of loss of estrogen during the postmenopausal state.

“Based on the study outcomes, we suggest floorball training as an efficient and motivating exercise modality that is suitable as a treatment-strategy for essential hypertension, even in postmenopausal women with no prior experience with floorball,” the authors concluded.

However, due to the low number of subjects, caution may be warranted in interpreting results.

Gunnarsson T, Ehlers T, Baasch-Skytte T, et al. Hypertension is associated with blunted NO-mediated leg vasodilator responsiveness that is reversed by high-intensity training in postmenopausal women. Am J Physiol Regul. Published online October 14, 2020. doi:org/10.1152/ajpregu.00170.2020

Postmenopausal women with elevated hypertension who participated in the high-intensity team sport of floorball, a form of indoor hockey, achieved a significant decrease in their blood pressure.

Team sport reduces hypertension in postmenopausal women

A prospective longitudinal study of copper intrauterine devices (IUD) inserted mostly by nurses in a maternity hospital in Brazil has found that the vast majority of women continued with the device at 1 year.

 also found that the IUD complications were the same as those commonly cited in the literature.

The 87 study patients, all aged 18 and over, were inserted with a copper IUD at a usual risk-maternity hospital in the city of Curitiba, Paraná, Brazil, between September and October 2017.

Overall, 38.6% of the women had the IUD inserted by physicians and 61.4% by nurses.

In total, 67.5% of participants said they chose a copper IUD because it was a non-hormonal method and 24.1% selected it because there was no risk of forgetting to administer it.

Two other reasons cited were an easy and practical method and safety.

Data were collected at 1 month after insertion via a return visit, followed by a telephone call at 6 and 12 months after insertion.

Upon returning for maternity consultation 1 month after IUD insertion, 69.9% of women did not present with any complications.

When asked about the adaptation to the method, 16.9% reported dysmenorrhea, 4.8% had menorrhagia, 4.8% had bacterial vaginosis and 1.2% reported dyspareunia.

The four participants who had bacterial vaginosis underwent recommended treatment and continued use.

At 6 months follow-up, 86.7% of women continued with their IUD and 13.3% reported discontinuing use.

Only one patient (1.2%) had her IUD fall out, 2 months after inserting the device. She also presented with dysmenorrhea and menorrhagia but said she intended to perform retry insertion.

Of the remaining 10 users (12.1%) at 6 months who experienced complications and chose or had to have their IUD removed, five (6.0% of the overall cohort) reported irregular bleeding as the cause for discontinuation (removing the device between 2 and 6 months after insertion); four (4.8%) reported not having adapted to the method due to the initial side effects, such as dysmenorrhea and menorrhagia and/or headache (removing the device between 2 and 5 months after insertion); and one (1.2%) had endometrial perforation 2 months after insertion.

Of the 11 participants who did not continue with the method after 6 months, five were inserted by physicians and six by nurses. None of these participants reported contraceptive failure with the IUD.

Most complications occurred in the first 6 months.

At 12 months, 85.5% of women continued with a copper IUD and 14.5% discontinued use.

The four major complaints at 12 months were dysmenorrhea (34.9% of the overall cohort), menorrhagia (24.1%), irregular bleeding (10.8%) and headache (3.6%).

Of the women continuing with the device, 32.5% were inserted by physicians and 53.0% by nurses.

Altogether, 62.7% of the cohort reported good acceptance and adaptation to a copper IUD. In addition, 56.6% complimented the fact that it was not hormonal and 55.4% would recommend the IUD to other women.

When participants were asked if they were satisfied with their IUD, 90% said yes and only 10% said no.

“Nurse practitioners are the ones who most perform IUD insertion,” wrote the authors, noting that training courses in IUD insertion for nurses at the national level and the expansion of social dissemination of this contraceptive method is crucial, which is available free of charge in Brazil.

Trigueiro TH, Ferrari JC, Souza SRRK, et al. Follow-up of copper intrauterine device insertion by nurses: a prospective longitudinal study. Rev Bras Enferm. Published online November 11, 2020. doi:10.1590/0034-7167-2020-0156.

The study in the Brazilian Journal of Nursing also found that the IUD complications were the same as those commonly cited in the literature.

Copper IUD insertion by nurses

“The reduced risk of ovarian cancer with the use of oral contraceptives is well established,” said senior author Jacques Balayla, MD, MPH, a clinician-scientist and Osler fellow in the Department of Obstetrics and Gynecology at McGill University in Montreal, Quebec, Canada. “We sought to determine whether other forms of contraception, namely the intrauterine device (IUD), accomplished the same goals.”

The authors searched the Medline, EMBASE, Google Scholar, Scopus, ISI Web of Science and Cochrane databases, as well as PubMed and the RCT (randomized controlled trials) registry, to conduct a systematic review and meta-analysis comparing ever-use vs. never-use of an IUD and the risk of subsequent ovarian cancer.

Of 431 records obtained, 9 met inclusion criteria: 5 case-control studies (a total of 2,232 cancer cases among 4,368 IUD users, with matched control ratios ranging from 1:1 to 1:2) and four cohort studies (a total of 269,045 patients).

Compared to never-use of an IUD, ever-use conferred a lower risk of ovarian cancer: estimated odds ratio (OR) 0.67; 95% confidence interval (CI): 0.60 to 0.74 (

Furthermore, this relationship remained significant when results were restricted to studies evaluating the levonorgestrel intrauterine system (LNG-IUD) alone: estimated OR 0.58; 95% CI: 0.47 to 0.71 (P < 0.0001, 

The same significant relationship also persisted when the analysis was stratified by study design, with an estimated OR of 0.64 (95% CI: 0.56 to 0.74) for case-control studies and an estimated OR of 0.71 (95% CI: 0.60 to 0.84) for cohort studies (

Only one of the nine studies (a cohort study) found an increased risk of ovarian cancer in IUD ever-users.

“An IUD is thought to act locally in the endometrial cavity, with minimal absorption of the hormones secreted into the circulation,” Balayla told 

. “The fact that a locally acting agent can have effects in adjacent organs was a surprising finding.”

The exact reasons why an IUD significantly reduces the risk of ovarian cancer need to be better elucidated, but the authors hypothesized three potential mechanisms: (1) mechanical barrier against potential carcinogenic agents; (2) decreased retrograde menstruation and displacement of endometrial cells; and (3) progesterone-induced benefit amongst hormonal IUDs.

“We already know the benefits of an IUD for contraception, for the treatment of abnormal uterine bleeding, and even for the reduction in rates of endometrial cancer,” Balayla said. “While the use of an IUD is not currently approved for the prevention of ovarian cancer, the findings of our study may point toward yet another benefit of the IUD that could be discussed during the clinical counselling of patients.”

Future studies will need to determine whether the known beneficial effects of an IUD are a function of duration of use, of a particular kind of device or specific tumor types, according to Balayla. “In the meantime, our current findings may serve clinicians to reassure and counsel patients about the added cancer advantage of IUDs,” he said.

Balayla reports no relevant financial disclosures.

Balayla J, Gil Y, Lasry A, et al.Ever-use of the intra-uterine device and the risk of ovarian cancer. J Obstet Gynaecol. Published online October 12, 2020. doi:10.1080/01443615.2020.1789960

IUD and risk of ovarian cancer

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Volume 65 No 11: The Technology Issue, November 2020

Team sport reduces hypertension in postmenopausal women

Copper IUD insertion by nurses

IUD and risk of ovarian cancer

S2E8: Skeletal dysplasia with David Abel, MD

Poll: Do you treat patients affected by skeletal dysplasia?