Before being treated by Defendant ob/gyn A, the plaintiff had seen Co-defendant ob/gyn B in January 2013 for worsening symptoms of prolapse. Her complaints included incomplete voiding, urinary frequency, nocturia, urgency two to four times per day, and some rare episodes of stress urinary incontinence (SUI). 

Dr. B found that the plaintiff had evidence of Stage II uterovaginal prolapse 1 cm past the hymen. His impression was uterine prolapse, cystocele, rectocele, and urinary incontinence, and a need to rule out voiding dysfunction. The plaintiff’s treatment by Dr. B continued through the winter of 2013, during which various surgical interventions were explained to her. She ultimately gave him consent for a laparotomy, supracervical hysterectomy, bilateral salpingo-oophorectomy (BSO), sacrocolpopexy with permanent mesh, possible cystocele and rectocele repair, and cystoscopy. 

The plaintiff underwent surgery with Dr. B at Codefendant Hospital on May 7, 2013. Dr. B discussed the risks of surgery with the plaintiff including possible bowel injury. He encountered significant scarring, which he stated might be secondary to previous obstetrical injury. He did not perform the sacrocolpopexy because of his intraoperative findings of a deep pelvis, pelvic adhesions, redundant bowel, and diverticular disease. In the setting of an obese woman with diabetes, risk of infection and mesh erosion was greater, therefore, he elected to perform a modified colpopexy. 

The plaintiff was on disability from May through July 2013 and Dr. B continued to treat her during that period. However, by the August 19, 2013 visit with Dr. B, it appeared that the plaintiff was having recurrence of prolapse. He had a long conversation with her but did not recommend any surgical intervention. The plaintiff’s last visit with Dr. B was on November 18, 2013. He noted she was having chronic constipation, and was not only bothered by vaginal protrusion, but there were days when she felt some discomfort. On exam, Dr. B noted excellent healing of the abdominal incision and no apical approach or cystocele. During maximal straining, a small Stage I rectocele and distal component 2 cm above the hymen was noted. There were no foreign bodies in the vagina and no antrocele. Dr. B instructed the plaintiff to do pelvic floor exercises and to lose weight. He noted that at that time he was very pleased with the results.

On February 24, 2014, the plaintiff presented to Nonparty ob/gyn C and his facility for an assessment of her recurring vaginal prolapse. Dr. C noted that she was a 62-year-old G4P3 who presented with a chief complaint of occasional urgency with leakage. She also admitted to frequency and nocturia but denied urinary leakage with cough, laugh or sneeze (SUI). She reported feeling a bulge and was status post-supracervical abdominal hysterectomy, uterosacral ligament suspension, and posterior repair done in May 2013 at Co-defendant  Hospital (by Dr. B).  Dr. C indicated that he reviewed those records and that Dr. B had originally consented the plaintiff for a mesh sacral colpopexy, but that intraoperatively, Dr. B decided against the use of mesh.

A review of systems and physical exam were generally within normal limits except that the exterior vaginal wall demonstrated a large cystocele to 1 cm past the introitus, cervix at the level of the introitus, and there was a large rectocele. Bedside cystometrics was also performed and demonstrated a fair sensation at 100; fullness 270, max capacity at 300 with a negative cough stress test, pretest postvoid residual (PVR) of 180, and post-test residue of less than 10.  Dr. C’s overall impression was that the plaintiff had a large recurrent prolapse, status post-uterosacral ligament suspension.

Dr. C indicated he had a “long discussion” with the plaintiff. He noted that uterosacral ligament suspensions have a success rate at best in the range of 60% to 80%. Sacral colpopexy would give her a success rate of close to 99%. His note also indicated that the plaintiff would consider having a sacral colpopexy as well as anterior and posterior repair. Dr. C also indicated that he took time to discuss the pros, cons, risks, benefits, success and failure rates of the proposed procedure as well as complications including but not limited to injury to bowel, urinary tract infection (UTI), blood loss, mesh erosion, new onset of incontinence, urinary retention, and need for additional surgery.  


	
	The plaintiff’s treatment with Dr. A began on June 2, 2014. At that time, she was evaluated for symptomatic vaginal prolapse for the past 10 months, which was affecting her lifestyle. Her current complaint was voiding 15 to 20 times per day and twice per night. Dr. A’s conclusion was vaginal vault prolapse post-hysterectomy. Options of conservative observation, pessary placement, and surgery were discussed in detail. Potential risks and complications were also discussed. The plaintiff agreed to undergo a minimally invasive sacrocolpopexy. 

On July 14, 2014, the plaintiff underwent a Pelvic electromyogram (EMG) and urodynamics, which showed that her bladder capacity was normal with sphincter coordination. There was urethral hypermobility with SUI. The plaintiff returned to Dr.  A’s office on August 18, 2014, and Dr. A suggested a laparoscopic vs. robotic sacrocolpoplasty with midurethral sling. The plaintiff had Stage 3 anterior wall vaginal prolapse (AWVP) and Stage 2 apical prolapse and underwent urethrosacral culpoplasty with Ethibond and Vicryl without sacrocolpopexy, anterior repair perineorrhaphy, supracervical hysterectomy, and BSO in May 2013. Comorbidities included hypertension, diabetes mellitus, hypothyroidism, gastroesophageal reflux disease, and atherosclerosis. She was postmenopausal. 

Dr. A documented an exhaustive discussion with the plaintiff regarding the potential risks and complications of the proposed surgery, which included, among other things, risk of infection requiring antibiotics and re-hospitalization, and risk of damage to adjacent organs including but not limited to the bladder, bowel, ureters, and nerves. The plaintiff also signed a general surgery consent form acknowledging that Dr. A explained the potential risks of the procedure in a way that the plaintiff could understand.   

On September 3, 2014, the plaintiff presented to Defendant Hospital for surgery. The procedure performed was diagnostic laparoscopy with lysis of adhesions, sacrospinous ligament fixation, anterior repair, laparotomy, enterotomy repair x 2 and cystoscopy.  Laparoscopic findings included dense adhesions noted between the small bowel and anterior abdominal wall extending from the umbilicus to the bladder. The adhesions penetrated into the fascia consistent with a ventral hernia and involved the rectal muscle. There were also adhesions between the colon and lateral sidewalls and the small bowel and bladder. Lysis of adhesions was performed for 1.5 hours. A questionable (non-circumferential) partial rectal prolapse was encountered. Cystoscopy revealed proper positioning of the mesh without perforation or ureteral obstruction. An Obtryx sling material was used. 

According to Dr. A’s operative report after the abdominal cavity was surveyed:


	“Dense adhesions were noted along the anterior abdominal wall between the small bowel, the omentum, and the anterior abdominal wall. Careful dissection was performed with the monopolar scissors mostly without heat, to lyse the adhesions for about 1.5 hours. During this dissection, as we uncovered the adhesions, we discovered that the bowel was densely adhered to the anterior abdominal wall fascia and rectus muscles. Also a 3 mm serosal tear was noted in the small bowel. This was tagged with a vicryl and colorectal was consulted. He agreed this needed oversewing and further lysis of adhesions and that this would be best achieved via an open incision. We converted to a midline incision (chosen based on where the adhesions were). The abdomen was insufflated as we made an incision with the knife and carried it down to the underlying layer of fascia to help protect the bowel

 At this point we connected the incision with the ventral midline hernia just inferior to the umbilicus and entered the peritoneal cavity. We extended the incision inferiorly taking care to avoid the bowel adhesions. At this point colorectal surgery scrubbed in and in running the bowel an enterotomy was identified with no frank spillage and he primarily repaired that with vicryl and then oversewed the previously identified serosal tear. He also assisted with the remaining lysis of adhesions. 

At this point, the decision was made to not proceed with the sacrocolpopexy due to the concern for a contaminated field due to the enterotomy. I stepped out to discuss the operative findings and plan with her husband and decision was made to proceed with native tissue repair.” 

A typed operative report by the Colorectal Surgeon noted that he was called intra-operatively to assess the small bowel. He further noted in his operative report that “during lysis of adhesion, an enterotomy was noted.” There was a serosal tear in the proximal ileum as well as a full-thickness enterotomy in the mid ileum, which was 25% circumferential. The serosal tear and the enterotomy were repaired with interrupted 3-0 Vicryl suture. There were no other intraoperative or postoperative complications and the plaintiff was admitted overnight for observation. 

On September 5, 2014, the plaintiff complained of mild soreness at the incision site. However, she was afebrile, voided, and tolerated liquids. She was then discharged home on Oxycodone, Motrin and Senna. She was instructed to continue all prior medications. No antibiotics were prescribed. 

The plaintiff followed up with Dr. A’s office on September 9, 2014. She reported that she was voiding, had a bowel movement, and was ambulating. On September 13, 2014

 the plaintiff was admitted to the Defendant Hospital with complaints of oozing from the vaginal incision site. Her vital signs were stable and she was afebrile with a pain score of 5/10. She reported 2 days of peri-incisional erythema and separation of the incision on the day of admission. She had called Dr. A’s office and Keflex was prescribed for presumed cellulitis.

The plaintiff had a visible 2-cm abdominal wall incision with 10-cm tunneling above the fascia. Purulent drainage was expelled, drained, and debrided and the wound was packed while in the emergency room. The plaintiff was admitted for wound infection and was started on wet-to-dry dressing changes, Ancef, and Bactrim. Over the next 2 days, her  erythema decreased with dressing changes and Gram stain of the drainage showed neither white blood cells nor bacteria. Cultures showed moderate 

. The dehiscence was noted to be 2.5 cm deep to fascia and 1.5 cm wide. However, the plaintiff remained afebrile without evidence of sepsis. She was discharged home on September 16, 2014 on oral clindamycin.    

 the plaintiff was seen by Dr. A after being hospitalized for a wound infection. However, the wound was slowly healing and measured 3 cm deep with some tracking superiorly. Dr. A noted that the plaintiff had no complaints of fever, chills, bulge or incontinence. She was to follow-up in 2 weeks, at which time a pelvic exam would be done.

 VNS called Dr. A’s office and reported that there was yellow-green discharge from the wound. However, there was no odor, increased drainage or fever. An office appointment was arranged for the next Monday. The plaintiff returned to Dr. A on September 29, 2014 for a follow-up visit. At that time, her wound was examined and repacked. On October 6, 2014, the plaintiff was seen for a follow-up visit for her wound and for complaints of urinary frequency. At that time, it was noted that her wound was healing and was 2 cm deep and 3 cm long. At the next visit on October 20, 2014

 Dr. A noted that the plaintiff’s wound was almost closed. No prolapse was appreciated on exam and estrogen cream was prescribed for atrophic vaginitis.

On October 27, 2014, the wound was noted to be closed and the plaintiff reported no pain or incontinence. At a follow-up visit on February 1, 2015, the plaintiff complained of double voiding and incomplete emptying; she was treated with Macrodantin. At her last reported visit with Dr. A, on March 16, 2015, she complained of rectal bulge (small hemorrhoid noted on rectovaginal exam), “occasional” fecal urgency and “some” incomplete bladder emptying. A bowel regimen was started and she was referred for pelvic floor exercises. On a form entitled “Patient Global Impression of Improvement,” the plaintiff indicated that her postoperative condition was “normal” and that when compared to her preoperative condition she was “much better.”  

On July 28, 2015, the plaintiff presented to her private ob/gyn, Dr. E, with complaints of a recurrent prolapse. However, Dr. E’s note includes no exam findings consistent with recurrent prolapse. On November 16, 2015, the plaintiff underwent right carotid endarterectomy at Codefendant University Hospital, which was complicated by transection of the carotid artery. Postoperatively she had a right middle cerebral artery infarction with left hemiparesis. There was no reference to any urologic complaints.

The plaintiff alleged that the defendants were negligent in performing a laparoscopy; in causing an enterotomy; in causing the need to perform an exploratory laparotomy and repair; in failing to properly and sufficiently plan the laparoscopy; in failing to perform appropriate preoperative testing to assess adhesions; and in failing to take all measures necessary to prevent any complications from the laparoscopy. Plaintiff argued the procedure should have been commenced open and opposed to laparoscopically. In addition, plaintiff contended Dr. B “botched” the first prolapse repair, leading to the cascade of events that necessitated future surgeries and complications.

As a result of the alleged negligence, the plaintiff asserted injuries including large recurrent prolapse, urgent urinary frequency, nocturia, and loss of services to her husband. 

The plaintiff testified that Dr. A advised her that when she started the procedure laparoscopically, they came into contact with numerous adhesions which no longer permitted her to perform the surgery as planned. In addition, as a result of the adhesions, her bowel was nicked and ultimately repaired intraoperatively. Since that surgery, she conceded she no longer experiences any type of urinary complaints. In addition, with respect to the prolapse, the plaintiff also testified that following Dr. A’s surgery in September 2014, she no longer experienced any type of bulging or prolapse. She did testify that she had a brief recurrence in or about April of 2015, however, it self-resolved. With respect to the claim for loss of consortium, she testified that following her surgery with Dr. A, her ability to have a physical relationship with her husband was not affected. It was clear that any significant injury she suffered was related to the stroke she suffered in November of 2015.

Dr. B testified that one of the reasons why he decided to do the modified colpopexy, as opposed to the sacrocolpopexy, was because the plaintiff had diverticular disease. According to Dr. B, the plaintiff had a good postoperative course and as of the last time that he saw her, she had a normal vaginal vault and excellent apical suspension.

Dr. A testified that from the time of their first meeting, the plaintiff was insistent on having a sacrocolpopexy. She nevertheless went through a full presentation of the various options available to the plaintiff, including pelvic floor therapy, placement of a pessary, and expectant management. The plaintiff refused those options. Alternative procedures discussed were colpocleisis; use of vaginal mesh; a vaginal approach using uterosacral ligament suspension; and sacrocolpopexy with mesh. 

Upon entering the abdomen, Dr. A testified she encountered dense adhesions and, therefore, she called Colorectal Surgery to assist with the lysis of adhesions. She spent 1.5 hours lysing adhesions. At some point she noted a 3-mm serosal tear in the plaintiff’s bowel. Colorectal Surgery recommended that they convert to an open procedure in order to lyse adhesions and inspect the bowels. Both the serosal tear and the enterotomy were repaired with sutures. She cautioned the patient preoperatively about the risk of adhesions and conversion.

We had expert support from Obstetrics and Gynecology, Urogynecology and Colorectal Surgery as to the indications for surgery, the consent provided, the surgical approach and technique, as well as the conversion to open and repair of enterotomies, which were known risks of the procedure and could not be predicted or prevented by testing preoperatively.
	 


	At the close of discovery, we moved for Summary Judgment (dismissal) as to our clients. So did counsel for Dr. B. Interestingly, the plaintiff’s counsel did not oppose our motions with an expert of his own, but instead tried to use our experts against each other to suggest that if sacrocolpopexy was not indicated when Dr. B operated, then it was a departure for Dr. A to perform that procedure. Alternatively, if it was indicated, then Dr. B departed by not performing it during the initial prolapse surgery. In reply, both defendants were able to use their experts to coordinate theories and display to the Court that there was no inherent contradiction between their respective positions. The Court did not accept the plaintiff’s arguments, found that defendants met their burden of proof entitling them to dismissal, and that the plaintiff’s failure to produce an expert affidavit in contravention of defendant’s positions was fatal to their claim.


	It can be tricky at times to coordinate defenses amongst codefendants whose treatment occurred at different stages of the patient’s care. Doing so, however, should be the primary objective, as a unified defense prevents the kind of blaming or finger-pointing that can weaken both defenses and lend weight and credibility to a plaintiff’s assertions. Here, both defendants were able to prove that their course of action at the time they undertook to treat the patient was appropriate, based upon not only the exercise of medical judgment, but the particular issues they were faced with respectively. Each physician was able to articulate their rationale for approach and decision-making in a way that enabled their retained experts to support their care, rather than blame the other for complications that proved to be known risks of surgery. Faced with a unified defense, the plaintiff could not find expert support for rebuttal.

Articles

In a case with multiple defendants, coordinating defenses should be the primary objective for trial.

Was this prolapse  properly managed?

Protecting pregnant women and their newborns by offering timely and effective vaccinations is a critical component of disease prevention, particularly given the rise of vaccine-preventable disease in the United States and around the globe. Studies show that when clinicians are knowledgeable about the benefits of vaccines and offer them to their patients, uptake of vaccination rises.

This is particularly true during pregnancy, when patients are concerned about vaccine safety and efficacy.

In this review, we provide an
	evidence-based summary of the vaccines that are recommended for women preconception, during pregnancy, and postpartum and provide counseling tips to help providers achieve the highest vaccine uptake rates possible.

The preconception period offers a unique opportunity to optimize a woman’s health for pregnancy and beyond. 


	Influenza infection during pregnancy has been associated with severe maternal illness, pregnancy loss, and preterm birth.

 Immunity confers significant benefits to both pregnant women and their offspring.

 Generally available for administration from late August through March of each year to correspond with the influenza season (timing may vary by region), the trivalent or quadrivalent, inactivated influenza vaccine should be given to all individuals older than age 6 months, including women considering pregnancy. Do not administer live vaccine (LAIV, Flumist) to women who may be pregnant but there is no contraindication to their family members receiving the live vaccine.


	Given the global measles outbreak, the Centers for Disease Control and Prevention (CDC) and American College of Obstetricians and Gynecologists (ACOG) recommend assessing measles immunity in addition to rubella immunity.

 The CDC recommends an evaluation of either a patient’s vaccine record or confirmatory measles serology to prove immunity (Table 1).

 While a single prior MMR dose may be adequate for some women, patients at high risk for exposure to measles should demonstrate proof of two doses. Many providers ask if the demonstration of rubella immunity from a prior pregnancy is adequate to confirm measles immunity. While rubella immunity is generally correlated with receipt of at least one MMR vaccine, that is not a valid surrogate for measles immunity. If the appropriate number of MMR doses has not been documented or the vaccine record is not available, measles serology can be obtained, and an MMR vaccine booster administered to patients with a negative Measles IgG antibody result. After receiving the MMR vaccine-a live, attenuated vaccine-women should wait 4 weeks prior to attempting pregnancy, given theoretical risks to the fetus with live vaccines.

 However, if pregnancy occurs inadvertently within the 4-week window, patients should be reassured that there have been no reports of fetal harm due to this exposure. 

Assessing rubella immunity has been a longstanding part of prenatal testing given the preventability of congenital rubella syndrome for those who have been adequately vaccinated with MMR. Therefore, women who are either measles non-immune or rubella non-immune should be vaccinated in the preconception period.  


	Given the significant risk of maternal and fetal harm with primary VZV infection during pregnancy, assessing a woman’s VZV immunity preconception will allow you to provide her with varicella vaccine if she is not immune. A history of chicken pox infection, evidence of VZV vaccination, or positive VZV serologies are all acceptable means to assess immunity.  For a woman without proof of immunity, a preconception VZV vaccine can protect her from life-threatening pneumonia and her fetus from congenital varicella syndrome. Because the vaccine for VZV is live attenuated, vaccination should be performed, at least 4 weeks prior to attempted conception given the theoretical concern for causing birth defects.

Other vaccines may be indicated, particularly in women who have medical illnesses that put them at high risk for
	vaccine-preventable illnesses. Obtaining a thorough preconception immunization history as part of routine care also may uncover adult women who have missed prior vaccination opportunities. 

Hepatitis B (HPV) and hepatitis A (HAV) 


	HAB and HAV immunity is particularly important for women planning pregnancy who are at high risk for these infections (Table 2). HBV vaccine is administered in a three-dose series (0, 1, and 4 months apart). The vaccine for HAV is inactivated and can be given pre-exposure as a two-dose series (6 to 18 months apart), or as post-exposure prophylaxis. These vaccines are recombinant and have not been associated with adverse fetal outcomes. Therefore, no waiting period is required after administration in the preconception period and they can be administered during pregnancy if needed or if the three-dose series has not been completed.


	The pneumococcal vaccine is indicated for adult women who are at high risk for serious complications from pneumococcus, such as individuals who smoke or who have asthma or diabetes.  Additional indications are summarized in Table 2.

 There are two pneumococcal vaccines. For adults with risk factors, the CDC recommends administering one dose of PCV13 followed by the PPSV23 dose at least 8 weeks later without a delay in conception.


	Vaccination against HPV is recommended to prevent new HPV infections and HPV-associated diseases, including cervical cancer. While this vaccine remains targeted to young adolescents, the Advisory Committee on Immunization Practices (ACIP) now endorses catch-up HPV vaccination for all individuals through age 26 years. Adults who have previously been infected with one or more HPV types can still benefit from protection for other types available in the vaccine. For adults aged 27 through 45 years, and at risk for new HPV infection, decisions around vaccination should be made using a shared clinical decision-making model

 HPV vaccination for patients older than age 15 should follow a three-dose regimen (0, 1 to 2 and 6 months). Counseling and guidance about the benefits of HPV vaccination are ideal for preconception women who plan for pregnancy in greater than 6 months. While the HPV vaccine is not recommended during pregnancy, inadvertent HPV vaccination during pregnancy is not associated with adverse events for a woman or her fetus.


	Incorporating vaccine administration as a routine part of prenatal care is key to protecting pregnant women and their offspring from vaccine-preventable diseases. Evidence-based strategies to build a robust vaccination program embedded within an obstetrical practice include: staff education for all individuals who encounter the patient (front desk, medical assistants, lab techs, nurses, midwives, and physicians), patient education in multiple languages, and standing-order sets.

When vaccines are not available within your office or clinic, encouraging women to receive needed vaccines at the pharmacy or through their employer is also important, but a less effective strategy. 

Vaccines that should be given to every pregnant woman during every pregnancy include influenza during flu season and Tdap.

 As noted previously, other vaccines may be given if women have high-risk comorbidities or are midway through a vaccine series. HAV, HAB, and the pneumococcal vaccine should be considered for administration during pregnancy based on a patient’s medical history and additional risk factors (Table 3). Obstetrical providers  who are knowledgeable about vaccine safety and efficacy and prepared to debunk myths about vaccines in pregnancy will have the highest rates of vaccine uptake (Table 4).


	Attention to vaccination continues as we care for women in the postpartum period. All women who are found to be rubella, measles, or VZV non-immune during pregnancy should receive these live-attenuated virus vaccines postpartum without concerns about lactation. Postpartum and lactating women who are age 26 or younger and who have not previously received HPV vaccination should have this series initiated. The vaccine may also be considered for women older than age 26 who are at risk for HPV exposure.

 Finally, postpartum and lactating women with risk factors (Table 2) who have not previously been vaccinated should receive HAV, HBV, and pneumococcal vaccines according to ACOG and CDC recommendations. 

Finney Rutten LJ, St Sauver JL, Beebe TJ, et al. Association of both consistency and strength of self-reported clinician recommendation for HPV vaccination and HPV vaccine uptake among 11- to 12-year-old children. 

Rutten LJF, St Sauver JL, Beebe TJ, et al. Clinician knowledge, clinician barriers, and perceived parental barriers regarding human papillomavirus vaccination: Association with initiation and completion rates. 

Martinello RA, Jones L, Topal JE. Correlation between healthcare workers’ knowledge of influenza vaccine and vaccine receipt. 

Shavell VI, Moniz MH, Gonik B, Beigi RH. Influenza immunization in pregnancy: overcoming patient and health care provider barriers. 

Goldfarb I, Panda B, Wylie B, Riley L. Uptake of influenza vaccine in pregnant women during the 2009 H1N1 influenza pandemic. 

ACOG Committee Opinion No. 732: Influenza Vaccination During Pregnancy. 

MÃ¸lgaard-Nielsen D, Fischer TK, Krause TG, Hviid A. Effectiveness of maternal immunization with trivalent inactivated influenza vaccine in pregnant women and their infants. 

Grohskopf LA, Alyanak E, Broder, KR et al . Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2019–20 Influenza Season. 

Measles & the MMR Vaccine: Recommendations Around Pregnancy, Including the Periconception and Postpartum Periods - UW Medicine Provider Resource. 

http://providerresource.uwmedicine.org/flexpaper/measles-and-the-mmr-vaccine-recommendations-around-pregnancy-including-the-periconception-and-postpartum-periods

Centers for Disease Control and Prevention. Measles: Evidence of Immunity. 

https://www.cdc.gov/measles/hcp/index.html#immunity

McLean HQ, Fiebelkorn AP, Temte JL, et al. Centers for Disease Control and Prevention. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). 

Marin M, GÃ¼ris D, Chaves SS, S et al.  Centers for Disease Control and Prevention (CDC). Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). 

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 86: Viral hepatitis in pregnancy. 

Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. 

Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). 

Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). 

Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices. Updated recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent pneumococcal polysaccharide vaccine (PPSV23). 

Pneumococcal Vaccination Summary | Who and When to Vaccinate | For Providers | CDC. 

https://www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html

. Published June 20, 2019. Accessed September 25, 2019.

HPV Vaccine Recommendations | Human Papillomavirus | CDC. 

https://www.cdc.gov/vaccines/vpd/hpv/hcp/recommendations.html

. Published June 27, 2019. Accessed September 25, 2019.

Committee Opinion No. 704 Summary: Human Papillomavirus Vaccination. 

Use of Standing Orders Programs to Increase Adult Vaccination Rates:  Recommendations of the Advisory Committee on Immunization Practices. 

https://www.cdc.gov/mmwr/PDF/rr/rr4901.pdf

Committee on Obstetric Practice, Immunization and Emerging Infections Expert Work Group. Committee Opinion No. 718: Update on Immunization and Pregnancy: Tetanus, Diphtheria, and Pertussis Vaccination. 

ACOG Committee Opinion No. 741: Maternal Immunization. 

When clinicians are knowledgeable about the benefits of vaccinations, vaccination rates among patients increase.

Perinatal vaccination: A practical guide for obstetric providers

Abnormal uterine bleeding (AUB) is common among premenopausal women.

 For many women, hormonal medications including estrogen and/or progestins is the mainstay of AUB management. Every provider, no matter how experienced with hormonal management of AUB, faces difficult clinical situations concerning the best hormonal regimen to choose in women at increased risk for venous thromboembolism (VTE). 

Incidence of VTE in women of childbearing age is 1 to 10 in 10,000 yearly.

 weight, smoking, certain clotting disorders, and use of combined hormonal contraceptives.

 Initially it was thought that estrogen alone increased VTE risk, however, it is now known that different progestins have varied VTE risk.

 This article reviews the current literature and guidelines to assist ob/gyns in evidence-based management of AUB with progestins, focusing on risk of VTE. Four patient cases are presented, each centered on a commonly used progestin for management of AUB in premenopausal women: the levonorgestrel intrauterine system (LNG-IUS), depot medroxyprogesterone, norethindrone acetate (DMPA), and megestrol acetate. Also included are guidance on patient counseling and a review of the available literature (Table 1). 


	A 25-year-old G0P0 with systemic lupus erythematosus (SLE) and positive anti-phospholipid antibodies presents to discuss management of heavy periods, a hemoglobin of 10.5 g/dL and a need for contraception. She denies a personal or family history of VTE. The woman doesn’t remember to take her other medications regularly and desires an option that lightens her cycle, while also providing longer-term effective contraception. 

You counsel your patient that the Centers for Disease Control and Prevention Medical Eligibility Criteria (CDC-MEC)

 guidelines characterize the LNGIUS as category 3 (risks generally outweigh benefits) in patients with SLE and positive antiphospholipid antibodies. However, you also educate her that citations behind the MEC recommendation are mostly based on a theoretical risk of VTE rather than studies of LNG-IUS use in her specific situation. Based on this patient’s positive antiphospholipid antibodies, the MEC guidelines recommend only one option for her: the copper IUD;

 however, with her heavy bleeding and mild anemia, it is not an ideal option. You counsel her that the literature does not demonstrate any increased risk of VTE with LNG-IUS use, in both low- and high-risk populations, and engage in shared decision-making. 


	The LNG-IUS is available in several versions, with its active progestin component levonorgesterol ranging from 13.5 to 52 mg. With use of the device, the stable plasma level of levonorgestrel is at most approximately 3% of the level seen with a levonorgestrel-containing combination oral contraceptive (COC) pill.

 The 52-mg LNG-IUS is approved by the US Food and Drug Administration (FDA) for contraception for up to 5 years and for heavy menstrual bleeding. There is no FDA warning for VTE risk on the package insert.

Multiple studies have evaluated use of the 52-mg LNG-IUS and VTE risk in a low-risk population.

 The largest was a 2009 national registry cohort study in Denmark involving non-pregnant women aged 15 to 49, with no history of cardiovascular disease or malignancy.

 The study evaluated 10.4 million woman-years and reported 4,214 VTE episodes. The authors concluded that compared to non-use of hormones, use of the 52-mg LNG-IUS was not associated with increased risk of VTE (RR 0.90; 95% CI 0.64-1.26).

 Two systematic reviews were conducted, one prior to and one including this article,

 both of which concluded that the 52-mg LNG-IUS does not increase VTE risk in low-risk populations.  

The relationship between the 52-mg LNG-IUS and VTE risk also has been evaluated in populations at higher VTE risk. A 2016 systematic review included nine studies of the the device in high-risk women with SLE, hypertension, smoking, thrombophilia, and history of VTE. The study concluded that there was no statistically significant increased risk of VTE in women using the 52-mg LNG-IUS in these high-risk populations.


	A 21-year-old G0P0 presents with amenorrhea for 6 months using intramuscular (IM) DMPA, which was started for menorrhagia. She is not sexually active and tells you she “doesn’t want a foreign object in my body.” Her friend was recently diagnosed with deep vein thrombosis after a car accident and leg fracture. Although your patient doesn’t have any other personal risk factors for VTE, she is concerned about her own VTE risk on an upcoming trip while using DMPA.   

You counsel your patient that a meta-analysis that found no increased VTE risk with other progestin-only agents did find a doubling in VTE risk with DMPA use.

 Despite this increased relative risk, the baseline risk of VTE is 1 to 10 per 10,000 yearly in a young, healthy population,

 so her absolute risk of VTE remains low on the order of 2 to 20 per 10,000. MEC guidelines are category 2 (benefits generally outweigh risks) for DMPA use in women with current VTE, history of VTE, or risk factors for it.

 You discuss with your patient that estrogen-containing options including COC pills would also be an option for her, however, they increase VTE risk 3-5 fold,

 which is a greater risk compared to progestin-only agents.


	Injectable DMPA is FDA-approved for prevention of pregnancy at a dose of 150 mg IM every 3 months.

 Contraindications listed on the package insert include active VTE and history of VTE.

A 2012 Dutch metaanalysis in women at low risk of VTE found no increased risk of VTE among overall users of a progestin-only contraceptive compared to non-users (relative risk 1.03; 95% CI 0.76 to 1.39). Importantly, the subgroup analysis of DMPA users demonstrated that, unlike other progestin-only options like the LNG-IUS and norethindrone, DMPA was associated with a doubling in VTE risk compared to that in non-users of hormones (relative risk 2.67; 95% CI 1.29 to 5.53).

Two studies assessed VTE risk with DMPA use in populations at higher VTE risk. The first found a trend toward an increased risk of VTE in smokers using DMPA (OR 7.0; 95% CI 0.4–138) compared to smokers not using hormones (OR 1.3; 95% CI 0.97–1.6), however, the confidence intervals were wide and the results were not statistically significant.

 The second is a case control study of women with Factor V Leiden mutations, which found no increased risk of VTE in women using other progestin-only agents, however, an increased risk of VTE was found in users of DMPA (OR 2.2; 95% CI 1.3-4.0).


	A 41-year-old G3P3 with a tubal ligation, migraine with aura, depression, and VTE during her third pregnancy presents to the Emergency Department with regular heavy menstrual bleeding. She has been bleeding for 5 days and is hemodynamically stable with moderate continued bleeding and a hemoglobin of 9.2 g/dL. 

You counsel your patient that due to her migraine with aura and history of VTE, estrogen-containing medications are not an option for her (MEC category 4, unacceptable health risk with method).

 However, for a rapid response and amenorrhea, contraceptive dosing of progestins may not be adequate. Available evidence shows that contraceptive doses of norethindrone acetate (0.35 mg) do not increase VTE risk. However, VTE data on higher doses of norethindrone acetate 2.5 mg to 15 mg commonly used for AUB

 are less clear. Your patient elects to start norethindrone acetate 2.5 mg and you both agree to start with the lowest dose that controls her bleeding. You schedule follow-up in your clinic to discuss longer-term options including the LNG-IUS and endometrial ablation. 


	Norethindrone acetate is FDA-approved for contraception at a dose of 0.35 mg, and for secondary amenorrhea, endometriosis, and AUB at a dose of 5 to 15 mg.

 The FDA does list “active deep vein thrombosis, pulmonary embolism or history of these conditions” as a contraindication for use of the higher doses of norethindrone but not for the contraceptive dose.

Several large studies on norethindrone acetate 0.35 mg used for contraception conclude that there is no increased risk of VTE with this dose.

 However, there are no studies on VTE risk with the higher doses of the drug used to manage AUB. Interestingly, a small study measured in vivo conversion of norethindrone acetate to ethinyl estradiol and concluded that 20 mg of norethindrone acetate may be equivalent to taking a pill containing 30 mcg of ethinyl estradiol.

 Prior small studies had varied results, with one suggesting no clinically significant conversion,

 another suggesting significant conversion at higher doses of norethindrone acetate,

 and a third suggesting rates of conversation of 6 µg ethinyl estradiol per 1 mg norethindrone acetate which could be significant based on dose.

 The in vivo impact of this conversion on VTE risk has not been evaluated, however, these findings could have implications for the VTE risk of the higher doses of norethindrone acetate used for AUB.

Oral medroxyprogesterone acetate is also used for AUB management at a dose of 5 to 10 mg, and is an option in this scenario. Little research has been done on VTE risk with oral medroxyprogesterone in premenopausal woman. A single relevant study was identified that included low-risk patients taking oral Provera; there was no association between VTE and progestin-only agents including oral medroxyprogesterone acetate, however, the size was small.

 Clearly, this is an area where more research is needed. 


	DD is a 52-year-old G2P2 obese, perimenopausal hypertensive and diabetic woman with irregular heavy bleeding. You perform an in-office endometrial biopsy, which demonstrates disordered proliferative endometrium. She is started on norethindrone acetate 5 mg daily, increased to 15 mg, however, she continues to bleed heavily.

You counsel your patient that some data, mostly from small studies in patients with active malignancy using MA in varying doses, did show a small increased VTE risk. However, these study populations are at inherently higher risk for VTE and may not be representative of this woman’s personal risk. There is very limited research on megestrol acetate for AUB. 


	Megestrol acetate is FDA-approved in doses of 40 to 320 mg/day for palliative treatment of advanced carcinoma of the breast or endometrium and treatment of cachexia in patients with AIDS.

 Regarding VTE risk, the FDA states that “thromboembolic phenomena including thrombophlebitis and pulmonary embolism (in some cases fatal) have been reported.”

Megestrol acetate is clinically used off-label for AUB, however, there are few data on this use. A retrospective chart review of 49 patients with AUB suggested efficacy of megestrol acetate in decreasing mean days of bleeding.

 A 2013 Cochrane review evaluating 1,602 patients using megestrol acetate for treatment of cachexia in patients with cancer, AIDS, and other pathologies found an increased relative risk of VTE of 1.84 (1.05- 3.18).

 Four studies have focused specifically on MA and VTE risk, including a retrospective case control study of 435 women with cancer using megestrol acetate as an appetite stimulant,

 a retrospective descriptive study in nursing home residents,

 a cohort study in 97 patients with advanced cancer receiving chemotherapy,

 and a randomized study of 179 patients with breast cancer patients whose disease failed to respond to tamoxifen.

 Three of these small studies suggest an increased risk of VTE with megestrol acetate use

 Because these studies all focused on patients at inherently higher risk of VTE, however, the results have very limited generalizability to a population of premenopausal women. 


	This review demonstrates the complexities of treating women with progestins for AUB. Shared decision-making between clinicians and their patients is indicated using the available data. The current data, clinical use, and expert opinion are often contradictory. This highlights the need for additional research on VTE risk of progestins used for management of AUB, especially in the context of other common risk factors for VTE, such as obesity, older age, and smoking.

Committee on Practice Bulletins-Gynecology. Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012 Jul;120(2):197-206.

Eichinger S, Evers JLH, Glasier A, et al.Venous thromboembolism in women: a specific reproductive health risk. Hum Reprod Update 2013;19:471-482.

Trenor CC 3rd, Chung RJ, Michelson AD, et al.Hormonal contraception and thrombotic risk: a multidisciplinary approach. 

Curtis KM, Tepper NK, Jatlaoui TC, et al.U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep2016;65:1-103.

Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. 

US Food and Drug Administration. Levonorgestrel-releasing intrauterine system. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021225s019lbl.pdf

Gaspard UJ, Romus MA, Gillain D, Duvivier J, Demey-Ponsart E, Franchimont P. Plasma hormone levels in women receiving new oral contraceptives containing ethinyl estradiol plus levonorgestrel or desogestrel. 

Lidegaard Ã, LÃ¸kkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ2009;339:b2890.

Tepper NK, Whiteman MK, Marchbanks PA, James AH, Curtis KM. Progestin-only contraception and thromboembolism: A systematic review. 

Mantha S, Karp R, Raghavan V, Terrin N, Bauer KA, Zwicker JI. Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis. 

Gialeraki A, Valsami S, Pittaras T, Panayiotakopoulos G, Politou M. Oral Contraceptives and HRT Risk of Thrombosis. 

US Food and Drug Administration. Depo-provera. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020246s036lbl.pdf.

US Food and Drug Administration. Oral provera. US Food and Drug Administration. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/011839s071lbl.pdf.

Bergendal A, Persson I, Odeberg J, et al.Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. 

US Food and Drug Administration. Norethindrone.  

https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/018405s023lbl.pdf

Chu MC, Zhang X, Gentzschein E, Stanczyk FZ, Lobo RA. Formation of ethinyl estradiol in women during treatment with norethindrone acetate. 

Klehr-Bathmann I, Kuhl H. Formation of ethinylestradiol in postmenopausal women during continuous treatment with a combination of estradiol, estriol and norethisterone acetate. 

Reed MJ, Ross MS, Lai LC, Ghilchik MW, James VH. In vivo conversion of norethisterone to ethynyloestradiol in perimenopausal women. 

Kuhnz W, Heuner A, HÃ¼mpel M, Seifert W, Michaelis K. In vivo conversion of norethisterone and norethisterone acetate to ethinyl etradiol in postmenopausal women. 

Barsoum MK, Heit JA, Ashrani AA, Leibson CL, Petterson TM, Bailey KR. Is progestin an independent risk factor for incident venous thromboembolism? A population-based case-control study. 

US Food and Drug Administration. Megestrol acetate. 

https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020264s017lbl.pdf

Muneyyirci-Delale O, Gupta A, Abraham C, Chandrareddy A, Bowers CH Jr, Cutler JB. Management of dysfunctional uterine bleeding based on endometrial thickness. 

Ruiz-GarcÃ­a V, LÃ³pez-Briz E, Carbonell-Sanchis R, Bort-MartÃ­ S, GonzÃ¡lvez-Perales JL. Megestrol acetate for cachexia-anorexia syndrome. A systematic review. 

Incidence of Venous Thromboembolism (VTE) in Patients Prescribed Megestrol for Appetite Stimulation | January 2017 | ACP. 

https://www.acponline.org/membership/medical-students/acp-impact/archive/january-2017/incidence-of-venous-thromboembolism-vte-in-patients-prescribed-megestrol-for-appetite-stimulation

Bolen JC, Andersen RE, Bennett RG. Deep vein thrombosis as a complication of megestrol acetate therapy among nursing home residents.

Ordu C, Pilanci KN, Koksal UI, et al.Can megestrol acetate induce thrombosis in advanced oncology patients receiving chemotherapy? 

ThÃ¼rlimann B, Castiglione M, Hsu-Schmitz SF, et al.Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Swiss Group for Clinical Cancer Research (SAKK). 

These four patient cases can help improve your decision-making about the best hormonal regimen for this population.

Progestins for AUB in women at risk of VTE

Experience in more than a quarter million women shows no significant association between use of powder in the genital area and ovarian cancer. The 

, are from the largest study to date on this topic.


	The conclusion was drawn by researchers based on a pool analysis of data from four large, US-based cohorts: 

Women’s Health Initiative Observational study 

(WHI-OS). The goal was to determine if there was a link between ever use of powder in the genital area and self-reported incident ovarian cancer. The new report includes updated data, more cases, and longer follow-up than the original research.

The authors noted that in the four studies, participants were asked about use of powder in the genital area in different ways. They therefore harmonized the data by categorizing the participants as having ever or never users. Long-term use was defined as at least 20 years or use at ages 10 to 13 years and also in the last year. Women were frequent users of powder if they had used in the genital area at least once a week, at least once a week in the last year, or “frequently” from ages 10 to 13.

Confounders in the four studies also were harmonized and included age at baseline, race, education, body mass index, parity, smoking status, hormone therapy use, and tubal ligation, hysterectomy, and menopausal status.  


	Across the studies, 39% of women commonly used powder in the genital area, with 53% ever use in WHI-OS, 41% in NHS, 27% in SIS, and 26% in NHSII. Rates of long-term use were 16% in WHI-OS and 6% in SIS and NHSII. Frequent use was reported by 27% of the women in NHS, 26% in NHSII, and 7% in SIS. The authors said that “there appeared to be a generational trend in use of powder in the genital area, with older cohorts more likely to report use.” Uses of powder also were more likely than non-users to be black (6% vs 3%), obese (26% vs 19%), and to be hysterectomized (22% vs 18%), and less likely to have used oral contraceptives (57% vs 64%).

Looking at incidence of ovarian cancer in the pooled sample, the authors found that among ever users, it was 61 cases per 100,000 person years versus 55 cases per 100,000 person years in women who had never used powder on their genital area. At age 70, the estimated risk difference was 0.09% (95% CI, -0.02% to 0.19%) and the estimated hazard ratio (HR) was 1.08 (95% CI, 0.99 to 1.17). The estimated HR for frequent vs never use was 1.09 (95% CI, 0.97 to 1.23) and for long-term vs never use, was 1.01 (95% CI, 0.82 to 1.25).

The researchers conducted subgroup analysis for 10 variables and none of the tests for heterogeneity were statistically significant for any of the comparisons. The estimated HR for the association between ever use of powder and ovarian cancer risk in women with a patent reproductive tract was 1.13 (95% CI, 1.01 to 1.26) but the 

 value for interaction comparing women with vs. without patent reproductive tracts was 0.15.


	Commenting on how powder might affect reproductive organs, the authors said that their analysis and a possible positive association in women with patent reproductive tract “lends support to the hypothesis that powder with or without asbestos could irritate and inflame the reproductive tract.” They emphasized, however, that the finding should be considered exploratory and hypothesis generating. While concluding that their study showed no statistically significant association between self-reported use of powder in the genital area and incidence ovarian cancer, they also acknowledged that it was underpowered to identify a small increase in risk.

Experience in more than a quarter million women shows no significant association between use of powder in the genital area and ovarian cancer.  

Vol 65 No 2

Was this prolapse properly managed?

Perinatal vaccination: A practical guide for obstetric providers

Progestins for AUB in women at risk of VTE

Does powder increase risk of ovarian cancer?