In case you missed it: Here are the top 5 posts this month

First US baby born after uterine transplant delivered in Texas

The first birth as a result of uterine transplant in the United States took place on Friday in Texas at the Baylor University Medical Center in Dallas. The women had undergone a live donor transplant and have received her uterus from Taylor Siler, 36, a registered nurse in the Dallas area.

The boy delivered by elective cesarean section is just named “baby number 9, as he is the 9th person in the world to be born out of transplanted uterus.

https://obgynupdated.blogspot.in/2017/12/first-us-baby-born-after-uterine.html

New approach to ovarian cystectomy: Transvaginal natural orifice transluminal endoscopic surgery

Natural orifice transluminal endoscopic surgery (NOTES) is a challenging minimally invasive procedure where ‘scarless’ abdominal surgeries are performed through an endoscope inserted through a natural orifice (mouth, anus, vagina, and urethra) and is considered as less invasive approach to laparoscopic surgeries. 

https://obgynupdated.blogspot.in/2018/01/new-approach-to-ovarian-cystectomy.html

ACOG updates its guidelines on Nausea and Vomiting in Pregnancy

The American College of Obstetricians and Gynecologists have updated its practice guidelines about managing Nausea and Vomiting in Pregnancy, published in the January issue of Obstetrics & Gynecology.

The guidelines replace the earlier document published in September 2015.

https://obgynupdated.blogspot.in/2017/12/acog-updates-its-guidelines-on-nausea.html

Stair-step ovulation induction protocols are not just limited to Clomiphene

Stair-step ovulation induction protocol with Letrozole is also as effective as stair-step method using Clomiphene Citrate, and has a slight edge over CC in obese patients reports the result of study published in March issue of Fertility and Sterility.

Stair-step ovulation induction protocols have shown to achieve ovulation induction in shorter time as compared to traditional protocols in women with PCOS. But, so far studies and clinical trials have mainly focused on Clomiphene Citrate(CC).

https://obgynupdated.blogspot.in/2017/12/stair-step-ovulation-induction.html

A simple, novel solution to identify and protect ureter during surgery

AllotropeMedical, a Houston based medical startup has devised StimSite, a novel, hand-held, single use device that precisely identifies ureter during surgery; thus, eliminating the need for ureteral stenting.

It is specifically useful in all gynecological, colorectal and oncosurgeries. Gynecological surgery accounts for 50% of all iatrogenic ureteric injuries.

https://obgynupdated.blogspot.in/2017/12/a-simple-novel-solution-to-identify-and.html

Iodine deficiency linked to delayed conception

Women who have moderate to severe iodine deficiency have a 46% less chance of getting pregnant as compared to women who have normal iodine levels says the results of the Longitudinal Investigation of Fertility and the Environment (LIFE) study, a population-based prospective cohort study published in recent issue of Human Reproduction.

This is the first study to investigate a link between iodine levels and chances of conception in women desiring to start a family.

The researchers interviewed and enrolled 501 women over a period of 5 years.  Urine samples of all the participants were collected at the start of the study for measuring iodine levels and these women reported on risk factors for infertility during the interview. The women were advised timed intercourse according to ovulation monitoring by various fertility trackers for a period of 1 year.

Pregnancy was detected with digital home pregnancy test around menstruation.

At 1 year, 72% women (332) conceived while 42 women could not, and the rest decided to leave the study.

It was seen that nearly 56% of women had sufficient iodine levels, while 44% of women had iodine deficiency, of whom nearly 25% samples were in range of moderate to severe iodine deficiency.

The researchers used fecundability odds ratio (FOR) to measure a couple’s chance of getting pregnant in a menstrual cycle. A FOR of less than 1 suggests that the couple will take longer time to achieve pregnancy, while FOR ratio more than 1 indicate a shorter time to pregnancy.

In this study, women with moderate to severe iodine deficiency had a 46% reduction in odds of conception as compared to women with adequate levels. (Adjusted FOR = 0.54)

According to National Institute of Health (NIH), RDA of iodine for pregnant and lactating women are 220 mcg and 290 mcg respectively, but no specific recommendation is made for women trying to get pregnant.  

According to WHO, a urinary iodine levels less than 150 mcg/L are considered insufficient while levels between 150–249 mcg/L indicates adequate iodine nutrition during pregnancy. About 30% of US women of childbearing age have iodine deficiency.

In pregnant women, iodine is necessary for brain development and is the most common cause of preventable mental retardation worldwide. It also causes miscarriage and stillbirths. Chronic, severe iodine deficiency in utero causes cretinism, a condition characterized by mental retardation, deaf mutism, motor spasticity, stunted growth, delayed sexual maturation, and other physical and neurological abnormalities.

This study does not prove causality, future studies are needed to replicate the findings.

It is also difficult to test women for iodine levels and give advice on iodine levels. The issue of iodine deficiency has not yet been addressed in women who are trying to conceive. 

The authors conclude that choosing a diet adequate in iodine is the key to avoid deficiency and some experts believe that consuming prenatal vitamins with iodine can address the problem of iodine deficiency in pregnancy.

Abstract 

Media courtesy: Mercola.com

EMT helps predicts the potential success of IVF cycle and neonatal birth-weight

An Endometrial Thickness(EMT) of less than 7.0 mm results in lowest livebirth rates of about 22%, reports the results of a large retrospective, single-center study involving 2827 women, published electronically in forthcoming issue of Journal Reproductive BioMedicine Online. These cohort of women underwent 3350 IVF cycles with fresh embryos over a period of 4 years.

Endometrial thickness is still a part of standard cycle monitoring during IVF but lacks robust evidence in its favor as a potential predictor of live births and success rate of the cycle.

Endocrine profile is being increasingly used in infertility practice to predict the outcome of various ART techniques.

Multivariate regression analysis showed that EMT was non-linearly associated with live birth rates.

Thickness between 7.0 mm and 9.0 mm resulted in about 30% live birth rate while thickness less than 7.0 mm was associated with only 22% live birth rate and a decrease in neonatal birth weight.

The results of the study reaffirm the value of measuring EMT as a prognostic tool for predicting live birth rates and neonatal weights in women undergoing IVF with fresh embryo transfer along with endocrine profile in late follicular phase.

Abstract

Media courtesy Journal of Human Reproductive Sciences

UTI in pregnancy: nitrofurantoin and trimethoprim-sulfamethoxazole overprescribed despite potential risks.

Nitrofurantoin and trimethoprim-sulfamethoxazole were commonly prescribed for pregnant women during first trimester in 2014, despite the potential risk associated with these antibiotics, reports the results of analysis of large insurance database by Center for Disease Control(CDC). These findings were reported in the Morbidity and Mortality Weekly Report(MMWR) by CDC issued January 12, 2018.

Pregnant women are routinely screened for UTI in pregnancy and receive antibiotics if they screen positive, because of foreseen serious complication later in pregnancy like pyelonephritis, preterm labor, low birth weight, and sepsis.

ACOG recommends to being selective in prescribing antibiotics during first trimester because of potential of birth defects with certain antibiotics. ACOG recommends that nitrofurantoin and trimethoprim-sulfamethoxazole should only be prescribed in early pregnancy when other antibiotics are found ineffective.

CDC gathered data of about 482,917 pregnancies from Truven Health MarketScan Commercial Database and analyzed it for prescription filled for antibiotics during the first trimester.

All pregnant women between aged 15–44 years with a diagnosis of a UTI from 90 days before LMP through the end of pregnancy were identified to be included in the study. UTI was defined according to the International Classification of Diseases Ninth Revision, Clinical Modification (ICD-9 CM) diagnosis code or presence of cystitis with an outpatient prescription filled.

Women with recurrent UTI or those who were admitted were excluded from study.

The data showed that 34,864 (7.2%) pregnant women had an initial outpatient UTI claim 90 days before or during pregnancy.  UTI was most common during the first trimester (40%) and least common in the third trimester of pregnancy.

Types of antibiotics prescribed differed according to pregnancy status of women, with fluoroquinolones and sulfonamides more commonly prescribed to women within 90 days before their LMP while nitrofurantoin, cephalosporins and penicillins were the drugs of choice during pregnancy.

The most common antibiotics prescribed during the first trimester were nitrofurantoin (34.7%), ciprofloxacin (10.5%), cephalexin (10.3%), and trimethoprim-sulfamethoxazole (7.6%).

This report has its own limitations because UTI was identified only based on codes and not lab reports, some women may have other concomitant infections for which these antibiotics were prescribed, the MarketScan sample was a convenient sample hence could not be generalized to whole of US populations and out of pocket payee women were not included in the study.

Inspite of these limitations,  the report shows that it is important for all healthcare providers to be aware of antibiotic recommendations in pregnancy and be aware that they are prescribing for two in women who are pregnant or who might get pregnant in coming months.   

CDC MMWR Report 

Sonographically measured fetal head circumference ≥35 cm at term increases the odds of cesarean delivery.

Sonographically measured fetal head circumference ≥35 cm, within a week of delivery increases the odds of unplanned cesarean section by 75% reports the results of multicenter observational study accepted for publication in American Journal of Obstetrics and Gynecology.

Currently, In US, one in every third baby is born by cesarean section and the high rate is a cause of concern for healthcare industry.

Physicians and patients will be greatly benefited by knowing more about factors that can predict the risk of cesarean section, in terms of better patient counselling and individual labor planning. Besides obstetrics factors, earlier studies have focused on estimated baby weight as a predictor of increased risk of operative and instrumental delivery.

This medical record based study looked at labor outcome of 11,500 primiparous women, presenting at term (37-42 weeks) with singleton fetuses in cephalic presentation for ultrasound with fetal biometry within one week of delivery.

All the patients who had an elective cesarean section were excluded from the study.

It was seen that head circumference ≥35 cm increased the odds of cesarean section by 2.5 times and increased the risk of instrumental intervention by 48%.

Increased head circumference and EFW ≥3900 also increased the risk of prolonged second stage of labor in the study cohort. At the same time head circumference ≥35 cm was significantly associated with improved Apgar score (p=0.01).

The authors concluded that Sonographic fetal head circumference ≥35 cm increased the second stage of labor and is also an independent risk factor for cesarean delivery.

Paired with EFW, increased head circumference ≥35 cm, can be useful for patient counselling and planning the labor. 

Abstract 

Intrauterine balloon tamponade for PPH significantly reduces the need for invasive procedures

Using Intrauterine balloon tamponade to control bleeding in postpartum hemorrhage lowers the use of invasive procedures by 84% in women with vaginal delivery reports the results of a large population-based retrospective cohort study published in January issue of Obstetrics and Gynecology Journal.

However, the same intervention did not lower the use of invasive procedures in women delivered by cesarean section.

This large, multicenter center study included 72,529 women delivered across 19 maternity units belonging to two perinatal networks in France.

The two networks either used Intrauterine balloon tamponade (pilot network) or used other methods for management of PPH.

Total .4% of women (298) had to undergo either pelvic vessel ligation, arterial embolization or hysterectomy.

A significant less number of women in the balloon tamponade group had to undergo invasive procedure as compared to the control group (3.0/1,000 vs 5.1/1,000, P<.01).

Similarly, the incidence of arterial embolization was significantly less in women in whom balloon was used to arrest PPH, for both vaginal (0.2/1,000 vs 3.7/1,000, P<.01) and operative mode of delivery (1.3/1,000 vs 5.7/1,000, P<.01).

After considering the confounding variables, it was seen that the risk of women undergoing an invasive procedure for PPH was 84% lower in women who underwent Intrauterine balloon tamponade as compared to other procedures used for control of PPH.   

Abstract

Media courtesy: slideshare.net

North American Menopause Society (NAMS) video series about important midlife health topics: New Treatment Option for Painful Intercourse

The North American Menopause Society (NAMS) is proud of its comprehensive video series for women on important midlife health topics. All the interviews in the series are hosted by NAM Board of Trustees Member and Immediate Past-President Dr. Marla Shapiro, a Canadian physician who led this exciting initiative. Dr. Shapiro is also the medical consultant for CTV News.

In this latest video, New Treatment Option for Painful Intercourse, Dr. Shapiro interviews Dr. Gloria A. Richard-Davis, NAMS Board Member, Division Director of Reproductive Endocrinology and Infertility at the University of Arkansas Medical Sciences and Medical Director of the Physician Assistant Program in Little Rock. Dr. Richard-Davis discusses a new nonestrogen, FDA-approved product (prasterone) and how it differs from other available products. She also answers questions about how to use it as well as how to initiate a conversation with your healthcare provider. 

Clomiphene compared with other drugs in terms of ovulation, EMT, pregnancy and live births: systematic review and meta-analysis

Ovulation induction with Clomiphene Citrate (CC) in women with WHO group II ovulatory disorders results in lower endometrial thickness (EMT) as compared to other regimens. The regimen also resulted in lower number of pregnancies and live births reports the results of systematic review and meta-analysis published in Journal Ultrasound in Obstetrics and Gynecology.

WHO group II ovulation disorders are defined as dysfunctions of the hypothalamic-pituitary-ovarian axis. This category includes conditions such as polycystic ovary syndrome (PCOS) and hyperprolactinaemic amenorrhoea. Around 85% of women with ovulation disorders have a group II ovulation disorder.

This systematic review and meta-analysis only focused on randomized control trials(RCTs) and included all those studies comparing CC with any other regimens and looked at EMT and rates of ovulation, pregnancy and live births.

The other regimens included in the study were Letrozole, CC plus metformin, CC plus N-acetyl cysteine (NAC), CC + nitric oxide (NO) donor and Tamoxifen.

The researchers selected 33 RCTs from 1718 articles that fitted the inclusion criteria amounting a total of 4349 women and 7210 ovulation induction cycle.

Maximum number (15) of RCTs compared CC with Letrozole. Overall the mean EMT was 1.39mm lower in CC group as compared to Letrozole. (WMD, −1.39; 95% CI, −2.27 to −0.51; I² = 100%), and women on CC had a 22% lower chance of pregnancy and 30% lower chance of live births. The ovulation rates were comparable between the two groups.

Only 2 RCTS were found comparing CC with CC plus metformin and no significant difference were noted in any of the outcome parameters between the groups.

When comparing CC with CC plus N-acetyl cysteine (NAC) and CC plus nitric oxide (NO) donor, EMT was lower in CC only group, along with ovulation and pregnancy rates.

When the CC regimen was compared with Tamoxifen, lower EMT and comparable ovulation and pregnancy rates were noted.

The authors concluded that in women with WHO group II ovulatory disorders, Letrozole seems to benefit these women more in terms of increased EMT, ovulation, pregnancy rates and live births. 

Whether the increase pregnancy rates and live births rates are due to increase in EMT has not been looked at in this study.

Abstract

Effectiveness of weight loss strategies to improve fertility in couples seeking treatments: A systematic review and meta-analysis of the evidence

Women who were on calorie restricted diet and exercised regularly during fertility treatments, are 59% more likely to become pregnant as compared to controls, says the results of a systematic review and meta-analysis published in November-December issue of Journal of Human Reproduction Update. The intervention also resulted in weight loss and improvement in ovulation rates.

However, the weight loss treatment didn’t bring down the rates of miscarriages.

According to WHO, “The number of obese adults increased from 100 million in 1975 (69 million women, 31 million men) to 671 million in 2016 (390 million women, 281 million men). Another 1.3 billion adults were overweight, but fell below the threshold for obesity.”

Male obesity also plays a part in reducing the fertility in couples. A study published in Nature also reported that couples with male’s BMI over 28 kg/m² exhibited a significantly lower fertilization rate, good-quality embryo rate and clinical pregnancy rate compared to their normal BMI counterparts.

A search of different databases, revealed about 40 studies over a period of 50 years, of which 14 were randomized control trials.

All the couples who were unable to conceive and have made a change in lifestyle with diet and exercises with the intention of conception were included in the study. Couple were excluded if they were not trying to achieve pregnancy. 

  

Two researchers independently extracted data and the study qualities were assessed using Cochrane Risk of Bias Tool for randomized trials, and a ratified checklist (ReBIP) for non-randomized studies.

Women who were eating a healthy calorie counting diet and exercising regularly were more likely to achieve pregnancy [risk ratio 1.59, 95% CI (1.01, 2.50)]. These women also showed an improvement in ovulation rates and lost weight through the program.

There was a paucity of weight loss interventions studies for men and couples together. Also, very few studies focused on barriers to weight loss.

Hence, a life style intervention of reducing fat and refined carbohydrates along with aerobic exercise should be the basis of programs designed for such couples.

Abstract

Media courtesy: http://www.medicalartcenter.com

Photo of the day: Three-dimensional sonography-based automated follicle count (SonoAVC) in polycystic ovarian morphology

Automated Volume Count software in three-dimensional volume of left ovary, depicting 67 antral follicles

Three-dimensional Sonography-based Automated Volume Count, GE Medical Systems (SonoAVC) could be a useful adjunct for follicular monitoring in patients with Polycystic ovarian syndrome (PCOS), with a significant saving in time and an accurate prediction over manual counts. 

SonoAVC was introduced in 2008 (GE Medical Systems, Zipf, Austria), and automatically identifies and counts follicles in a given ovarian volume because of hypoechoic nature against hyperechoic ovarian tissue background.

SonoAVC software is either integrated into the ultrasound device or it can be installed separately on a PC for the offline analysis of data sets obtained using an ultrasound device from the same manufacturer. Each volume has its own color, making SonoAVC an ideal tool for studying follicular development within the ovary.

Here is a beautiful picture of the day published on January 3, 2018 in the Journal Ultrasound in Obstetrics and Gynecology, which depicts the stark contrast between Grayscale two-dimensional ultrasound images showing follicles vs. automated follicle counting using Sonography-based Automated Volume Count software in three-dimensional volume of left ovary, depicting 67 antral follicles.  

Grayscale two-dimensional ultrasound images showing follicles

automated follicle counting using Sonography-based Automated Volume Count software

Technique of using SonoAVC on the Voluson E8 ultrasound system:

• A transvaginal ultrasound is performed using a 3D imaging probe (RIC 5-9 or RIC 6-12)

• Optimize the gain and harmonics for optimum image quality

• Select 3D imaging mode, adjust quality settings

• Adjust volume angle to include entire ovary and acquire volume

• Adjust 3D box over area of interest

• Select SonoAVC to evaluate the ovarian follicles

• Increase or decrease growth or follicular separation

• Select follicles manually if they are not identified

• Display report and chart

Full-Text of Journal Article 

Higher Topiramate dose in early pregnancy linked to increased risk of oral cleft

Use of Topiramate in early pregnancy for treating epilepsy is associated with nearly 8 times higher risk of oral clefts in newborn reports the results of a large population based cohort study published December 27, 2017 in journal Neurology.

The observed association was not very strong for lower doses of topiramate used for treating migraines and bipolar disorder.

A diagnosis of oral cleft includes cleft lip and cleft palate.

Previous studies have demonstrated a 5-fold increased risk of oral cleft in women taking around 200 mg of topiramate daily for epilepsy, but the association was unclear about consumption of lower dose.

To assess the risk of oral dose, the investigators analyzed a large cohort of 1,360,101 pregnant women with a live-born infant enrolled in Medicaid from 3 months before conception through 1 month after delivery over a period of 10 years. 

The prescription information was obtained from nationwide Medicaid Analytic eXtract (MAX) which keeps a record of all diagnoses and procedures and prescription filled outside hospitals.

The analyses of data identified 2425 women who were exposed to topiramate in early pregnancy as shown by atleast one filled prescription of the drug in first trimester.

The neonatal outcome for this cohort was compared to a reference group of 1,322,955 pregnant women who did not fill prescription for topiramate or other anticonvulsant drugs.

The multivariate analysis included many potential confounders like maternal age, race, topiramate indication (epilepsy, migraine, bipolar disorder, pain condition), obesity, smoking, comorbidities, concomitant medications, and overall health status.

Regression analysis showed that women with topiramate consumption in early pregnancy are 3 times increased risk of giving birth to a baby with oral cleft, as compared to women who have never taken the drug for any indication.

Risk was also assessed for consumption of another anticonvulsant medication, lamotrigine in first trimester. The risk with lamotrigine was only slightly more as compared to non-exposed population and the patients using topiramate were nearly 2.5 times at increased risk of oral clefts as compared to lamotrigine.

Women with epilepsy were nearly 8 times increased risk of oral cleft as compared to non-exposed.

Lead author, Dr Hernandez-Diaz, MD, professor of epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts said, "Our best estimate is that women with epilepsy using 200 mg or more of topiramate have around an 8-fold increased risk, and those using lower doses had a twofold or lower risk. The results suggest that the risk with lower doses, if it is there, is much less than for higher doses."

The researchers carried out multiple sensitivity analyses, with different doses of topiramate and window of exposure, but the association between topiramate and oral clefts remained the same.

The study confirms the results of earlier studies and stress upon the fact that “dose does matter.” The risk ratio for oral clefts for > 100 mg of topiramate was nearly 5 times more than that of < 100 mg.

In addition, topiramate does interfere with oral contraceptives and may be responsible for many unplanned pregnancies because of contraceptive failures. Hence, women who are on topiramate and do not want to conceive should additionally use a barrier method of contraception.

The study limitations include poor socioeconomic status of women (which itself is a risk for oral clefts), and not controlling for folic acid use.

Women with anti-epileptic medication should take folic acid which reduces the chances of oral clefts. 

But sometimes it is prescribed off-label to treat obesity and control weight gain.  In 2012, the United States Food and Drug Administration (FDA) approved topiramate in combination with phentermine (Qsymia) to treat weigh gain issues. 

Abstract

FDA press release

New approach to ovarian cystectomy: Transvaginal natural orifice transluminal endoscopic surgery

self constructed vNOTES glove port in low resource settings

Natural orifice transluminal endoscopic surgery (NOTES) is a challenging minimally invasive procedure where ‘scarless’ abdominal surgeries are performed through an endoscope inserted through a natural orifice (mouth, anus, vagina, and urethra) and is considered as less invasive approach to laparoscopic surgeries. 

NOTES is considered a logical next step in evolution of minimal invasive surgery, and the first NOTES procedure in humans is often considered to be a transgastric appendectomy performed in India in 2006 which was presented but not reported in manuscript form.

vNOTES is a natural orifice surgery performed through vaginal route. A look into history reveals that gynecologists have been performing colpotomies since years, adding their valuable experience towards NOTES surgeries and subsequent closure.

A recently published paper in forthcoming issue of Fertility and Sterility have demonstrated a new technique of performing ovarian cystectomy by this route and reports the technique and results of small study involving 14 patients.

The study was conducted at Gynecology department of non-university teaching hospital in Belgium.

All patients were placed in lithotomy position and under general anesthesia, a one-inch posterior colpotomy incision opened the pouch of Douglas.

vNOTES port was inserted through the incision, pneumoperitoneum was created by CO2, and the ovarian cyst was identified. Conventional endoscopic instruments and standard endoscope was used to dissect the cyst from the ovarian cortex by blunt and sharp dissection. Hemostasis achieved by bipolar forceps and cyst removed by bagging it in endobag through the colpotomy incision, which was closed by absorbable sutures.

All 14 patients underwent a successful fertility sparing cystectomy via the vNOTES procedure, without any complications or need for converting into open surgery.

The mean age of patients was 38 years, BMI= 24.7, cyst diameter = 45mm and mean parity = 2. The average surgical time was 37 minutes with only one patient having a history of previous pelvic surgery.

Nine patients were sent home within 12 hours and the rest within 30 hours of surgery.

The authors concluded, “Transvaginal natural orifice transluminal endoscopic surgery provides a new, less invasive approach for performing an ovarian cystectomy. This first IDEAL (idea, development, exploration, assessment, long-term study) stage 1 study confirms the feasibility of vNOTES ovarian cystectomy although it remains a novel approach that requires further investigation. It can provide improved patient comfort and better cosmetic results.”

Earlier studies involving small sample sizes have also reported successful performance of hysterectomies and uterine adnexal surgeries by transvaginal NOTES.

Abstract

Here is the video demonstrating the actual procedure.

FDA approves first generic version of Allergan's Estrace® estradiol vaginal cream

Global pharmaceutical giant  Mylan announced the U.S. launch of Estradiol Vaginal Cream USP, 0.01%, the first generic version of Allergan's Estrace® Cream. Mylan received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated in the treatment of vulvar and vaginal atrophy.

Mylan is one of the few companies that have Estradiol as an option across four delivery systems – cream, gel, transdermal patch and tablet.

Mylan President Rajiv Malik added in a press release, "Topicals like Estradiol Vaginal Cream are a great example of Mylan's ability to bring to market complex products. We have made substantial investments in research and development of these difficult-to-develop medicines and believe this provides long-term sustainability for our business."

Estradiol vaginal cream is often prescribed as topical treatment for postmenopausal vulvovaginal atrophy and had U.S. sales of approximately $449 million for the 12 months ending Oct. 31, 2017, according to IQVIA.

Mylan’s Press Release