At least one year is the ideal pregnancy spacing time for the health of mother and baby

  

One to one and a half year is the ideal spacing time between pregnancies according to researchers from the University of British Columbia (B.C.) and the Harvard T.H. Chan School of Public Health.

The study found an increased risk of premature births, maternal morbidity and mortality, and adverse neonatal outcome following an interpregnancy interval of fewer than 12 months in women of all ages. However, women who were 35 or more were at increased risks of maternal mortality or severe morbidity, while women aged 20 to 34 years were at increased risk of preterm labor and adverse fetal and infant outcomes.

In this large cohort study published online October 29 in JAMA Internal Medicine, the researchers looked at data from 148,544 pregnancies in B.C. to examine the relationship between interpregnancy interval and adverse pregnancy. The data was gathered from billing codes, hospitalization data, birth records, prescription data for infertility information, and census records for a period of 10 years (2004 to 2014).

The study is the most extensive and in-depth evaluation of the relationship between pregnancy spacing and maternal age. Currently, it is unknown whether older women face the same risk as younger women because of a shorter interpregnancy interval.

Women aged 35 and more who conceived within six months of a previous birth, faced 1.2 percent risk (12 cases per 1,000 pregnancies) of maternal mortality or severe morbidity (mechanical ventilation, blood transfusion >3 U, intensive care unit admission, and organ failure). Keeping an interpregnancy interval of 18 months, however, reduced the risk to 0.5 percent (five cases per 1,000 pregnancies).

For younger women, who conceived within six months of last childbirth, the researchers found an 8.5 percent risk (85 cases per 1,000 pregnancies) of spontaneous preterm birth, but the risk dropped to 3.7 percent (37 cases per 1,000 pregnancies) if the women waited 18 months before the next conception. 

Among older women, the risk of spontaneous preterm labor was about six percent (60 cases per 1,000 pregnancies) at the six-month interval, compared to 3.4 percent (34 cases per 1,000 pregnancies) at the 18-month interval.

“Our study found increased risks to both mother and infant when pregnancies are closely spaced, including for women older than 35,” said the study’s lead author Laura Schummers in a University of British Columbia news release. Dr. Schummers is a postdoctoral fellow in the UBC department of family practice who carried out the study as part of her dissertation at the Harvard T.H. Chan School of Public Health. “The findings for older women are particularly important, as older women tend to more closely space their pregnancies and often do so intentionally,” she further added. 

Senior author Dr. Wendy Norman, associate professor in the UBC department of family practice, said these findings of a shorter optimal interval are encouraging for women over 35 who are planning their families.

“Older mothers for the first time have excellent evidence to guide the spacing of their children,” said Norman. “Achieving that optimal one-year interval should be doable for many women and is clearly worthwhile to reduce complication risks.”

JAMA Internal Medicine Full Text

UBC News

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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

A revolutionary personal fertility sensor that sends you a message- “You are about to ovulate”

A Medical Device Premier Innovation summit was held recently at Minneapolis, MN by MedTech Strategist in association with The Medical Alley Association. About more than 40 start-up and emerging medical companies presented their technologies and devices at the summit.

Among the display was “Priya”, a vaginal temperature sensor that is being developed to wirelessly capture your continuous core temperature to detect the subtle changes that occur PRIOR to ovulation. 

Priya is developed by Prima-Temp, a medical device and technology  company situated in Boulder, CO, USA.

Priya is currently undergoing clinical trials, the intravaginal ring directly sends the temperature data to Priya App on the patients’ smartphone. When the subtle fall in temperature before ovulation is detected, the smartphone alerts the women.

Priya is an intravaginal ring made from medical-grade silicone form-factor and have a wireless continuous temperature sensor inserted within it. It’s dimensions and flexibility are similar to Estring®. Women are using these contraceptive vaginal rings or estrogen containing rings since may years. Prima-Temp just replaced the medications with a very sensitive sensor that measures core body temperature. Currently an algorithm is being tested to detect the DIP in temperature prior to ovulation.

This device has no extra monitor, urine strips or other extra parts that needs to be attached or monitored. The patient only needs to pair the ring with the app on the smartphone and insert the ring in the vagina.

Unlike the Basal Body Temperature (BBT), Priya monitors the internal core temperature continuously, which has been shown to more precise than oral or skin temperature. Based on this continuous core monitoring, the algorithms developed for Priya have been shown to achieve a 99% sensitivity for detection of ovulation, with a 99% percent accuracy in clinical trials.

Women’s body shows a striking diurnal variation and exhibit a pattern that is has been established as highly reliable marker for circadian rhythm. This pattern shows a distinct dip in body temperature 48- hours period prior to ovulation which is detected by the continuous monitoring by the ring sensors.

Trak fertility tracker, a breakthrough in at home sperm count testing launched.

SandstoneDiagnostics, a company based at Livermore, CA has launched Trak, a revolutionary new approach to male fertility that helps men test, learn and try to improve their sperm count over time. 

Many couples simply delay fertility treatment because the male partner is not comfortable in getting a semen analysis in the laboratory. Well, Trak not only measures sperm count based on current world health organization (WHO) guidelines and clinical research, from the comfort and privacy of your home, but it also offers you advice to improve the reproductive health.

This easy to use, first FDA cleared Trak engine uses centrifugal separation technique to isolate and quantify sperm count. The results are displayed like a thermometer reading as Low, Moderate or Optimal for conception.

click to enlarge

The kit that is available on Amazon, costs 199 $ for four testing sets. It is mailed to your doorsteps in discrete package and each set includes a collection cup, a dropper, a stick that the company calls a prop, and two seals. Shop At Home Male Fertility Testing System by Trak

Simultaneously, set up the Trak app on your smart phone and have to feed in answers to simple life style questions. The app will give you a basic score and combined with the sperm test results, you get information to make changes in your life style to improve your low results.

Many other at home sperm count testing devices are available but the combination of centrifugal system and app to improve reproductive health gives it an edge over other devices. 

Here is a video about how the test works.

Media Courtesy: https://trakfertility.com

Vitamin D and Human Reproduction—Evolving perspectives

We are all well versed with the role of Vitamin D in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. Its deficiency is linked to many chronic diseases of the cardiovascular and metabolic systems.

Evidence from animal and human studies suggests that vitamin D plays a very important role in human fertility and neonatal development. This steroid hormone has Vitamin D receptors (VDR) at multiple sites in the body including ovary, particularly the granulosa cells, endometrium and placenta.

It plays a very important role in ovarian steroidogenesis. [1] It deficiency contribute to development of insulin resistance and impaired glucose metabolism in patients with Polycystic Ovary Syndrome (PCOS). Therapeutic efficacy of supplementation with Vitamin D to improve insulin resistance, bring about ovulation and regularize menstruation in PCOs patients have been documented.[2] [3]

Observations also shows that lower 25(OH)D levels put women at higher risk of developing uterine fibroids, both in black and white ethnicities. In these women, the growth and size of the fibroid is also directly related to decreased levels of Vitamin D. Animal studies and human in vitro studies have shown the beneficial effect Vitamin D supplementation in inhibition of development and/or growth of uterine fibroids.[4] [5]

A recent study by Harris HR et al demonstrated that women within the highest quintile of Vitamin D blood values have one fourth the risk of developing endometriosis as compared to those in lowest quintile.[6]

It also plays a role in Body Mass Index (BMI) as per a recent meta-analysis, every 10% increase in BMI leads to 4% decrees in Vitamin D concentration.[7]

It’s role in male reproductive physiology is well documented by the fact that it’s level directly correlate with sperm motility and morphology.

As per Hill’s criteria a causal relationship between Vitamin D deficiency and negative outcome in IVF is explained but further research into knowing the magnitude of association is needed.[8]

A systemic review and meta-analysis by Lerchbaum E and Obermayer-Pietsch B published in Eur J Endocrinol May 1, 2012 concludes that Vitamin D plays an important role in Human reproduction and advocates the need of further research in therapeutic benefits of Vitamin D supplementation in such patients.  

Another review by Vanni et al published in the Reproductive Biology and Endocrinology, 2014 emphasizes the importance of supplementation of Vitamin D in IVF settings because consisting evidence documenting the increase incidence of gestational diabetes, IUGR, pre-eclampsia and preterm births in patients deficient in Vitamin D.[9]

The authors opine that although drastic improvements in reproductive failure may not be achieved solely by supplementing Vitamin D, but its addition to any fertility regimen is cheap, effective and without any side effects. It is easily correctable by simple oral supplementation.

Dosage up to 4000 IU is safe, without any side effects and effectively improve maternal vitamin D status. [10]

Results of double blind randomized trial entitled “Vitamin D during IVF” is still awaited.[11]

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[1]Anagnostis P, Karras S, Goulis DG: Vitamin D in human reproduction: a narrative review. Int J Clin Pract. 2013, 67 (3): 225-235

[2] Selimoglu H, Duran C, Kiyici S, Ersoy C, Guclu M, Ozkaya G, Tuncel E, Erturk E, Imamoglu S: The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome. J Endocrinol Invest. 2010, 33 (4): 234-238.

[3] Wehr E, Pieber TR, Obermayer-Pietsch B: Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest. 2011, 34 (10): 757-63.

[4] Bläuer M, Rovio PH, Ylikomi T, Heinonen PK: Vitamin D inhibits myometrial and leiomyoma cell proliferation in vitro. Fertil Steril. 2009, 91 (5): 1919-1925.

[5] Halder SK, Osteen KG, Al-Hendy A: Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and −9 in human uterine fibroid cells. Hum Reprod. 2013, 28 (9): 2407-2416.

[6]  Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA: Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am J Epidemiol. 2013, 177 (5): 420-430.

[7] Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Kiraki LT, Cooper JD, Dastani Z, Li R, Houston DK, Wood AR, Michaëlsson K, Vandenput L, Zgaga L, Yerges-Armstrong LM, McCarthy MI, Dupuis J, Kaakinen M, Kleber ME, Jameson K, Arden N, Raitakari O, Viikari J, Lohman KK, Ferrucci L, Melhus H, Ingelsson E, Byberg L, Lind L, Lorentzon M, et al: Causal relationship between obesity and vitamin D status: bi-directional Mendelian randomization analysis of multiple cohorts. PLoS Med. 2013, 10 (2): e1001383-

[8] Hill AB: The environment and disease: association or causation?. Proc R Soc Med. 1965, 58: 295-300.

[9] Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O’Beirne M, Rabi DM: Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ. 2013, 26 (346): f1169-

[10] Wagner CL, McNeil R, Johnson DD, Husley TC, Ebeling M, Robinson C, Hamilton SA, Hollis BW: Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: a combined analysis. J Steroid Biochem Mol Biol. 2013, 136: 313-320.

[11] https://clinicaltrials.gov/ct2/show/NCT01019785

Cleveland Clinics performs first Uterine Transplant from deceased donor in U.S.

The surgeons at Cleveland clinic performed first uterine transplant in U.S. this week.

Earlier in November 2015, Cleveland clinic announced a clinical trial that involved performing 10 uterine transplants in women with Uterine Factor Infertility (UFI).

About 1 in 4,500 women in the United States is born without a uterus - a condition known as Mayer-Rokitansky-Küster-Hauser syndrome, according to the NIH.

UFI is an irreversible condition affecting 3-5% of pregnancies worldwide. "Women who are coping with UFI have few existing options," Tommaso Falcone, chairman of the Department of Obstetrics-Gynecology at Cleveland Clinic, said when the clinical trial was announced. "Although adoption and surrogacy provide opportunities for parenthood, both pose logistical challenges and may not be acceptable due to personal, cultural or legal reasons."

The first two International attempts on Uterine Transplant were unsuccessful due to organ rejection. Finally a team of Doctors in Sweden were able to treat the mild organ rejection. The University of  Gothenburg team  led by Dr. Mats Brännström   achieved its first birth in September 2014. To date, the Swedish group has performed nine uterus transplants, achieving five pregnancies and four live births.

In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy.

Uterine Transplant is a complex process involving multiple steps. Each Candidate selected for the transplant undergo a extensive medical evaluation and psychological counseling, and her candidature has to be approved unanimously by the team of experts in the field.

According to the team at Baylor hospital, Dallas:

 

 

The selection criteria for the recipient are :

· Women with uterine infertility
· Ages 20-35, with working ovaries
· Body mass index of less than 30
· Cancer-free for at least five years
· No history of diabetes
· Non-smoker

The criteria to be a donor are:

  Ages 65 and younger
· At least one full-term delivery
· Body mass index of less than 30
· Cancer-free for at least five years
· Test negative for HIV, herpes and hepatitis B and C

According to the Cleveland clinic, once a woman is selected for the transplant she has to follow the following protocols:

• Her ovaries are stimulated to produce multiple eggs, starting the in vitro fertilization (IVF) process.
• Her eggs are retrieved, fertilized with sperms in a laboratory, and 6-8 embryos are frozen.
• Lifebanc, an organ procurement agency, begins the search for a donor between 18-40 years of age.
• The donor’s next-of-kin signs an informed consent for uterus donation.
• The donor uterus is removed along with the uterine arteries and   transplanted within six to eight hours into the patient’s pelvis.
• Over 12 months, the transplanted uterus fully heals.
• Women who receive the uterus transplants will not be able to become pregnant without ARTs, because the transplanted uterus will not be connected to their fallopian tubes, where normal fertilization takes place.
• One year after transplant, the frozen embryos are then thawed and implanted, one at a time, into the patient until she becomes pregnant.
• During her pregnancy, she takes immunosuppressant drugs.
• She is monitored by a high-risk obstetrics team throughout pregnancy and delivery.
• She has a monthly cervical biopsy to check for organ rejection.
• The baby is delivered by cesarean section.
• After one to two babies, she has a hysterectomy to remove the transplanted uterus.
• Her anti-rejection drugs are stopped after hysterectomy to reduce long-term exposure to transplant medications.

Andreas Tzakis, MD, the transplant surgeon at the Cleveland clinic says “It is critical that the risks for uterus transplant, which is not lifesaving, are no greater than the risks for other transplants. Like transplants of the face and extremities, uterus transplant is considered life-enhancing rather than lifesaving.”

He further adds “Unlike any other transplants, they are ‘ephemeral,” he says. “They are not intended to last for the duration of the recipient’s life, but will be maintained for only as long as is necessary to produce one or two children.”

References:

http://www.livescience.com/52799-uterus-transplants-cleveland-clinic.html

http://www.dallasnews.com/lifestyles/health-and-fitness/health/20160129-baylor-dallas-to-become-one-of-first-u.s.-hospitals-to-offer-uterine-transplants.ece

http://www.reuters.com/article/us-ohio-transplant-idUSKCN0VZ0O7