What is Glucomannan?

 What is  Glucomannan?

Recently, glucomannan has been introduced as supplement for insulin resistance treatment.Glucomannan is a high-molecular-weight polysaccharide obtained from tubers of Amorphophallus konjac: it consists of molecules of D-glucose and D-mannose, and it is soluble and absorbs water up to 200 times its weight.Glucomannan exerts its activity by increasing the viscosity of food bolus during digestion: it creates a viscous gel that makes the bolus smooth and soft, and it forms a nondigestible coating around food particles

Hyper homocysteinaemia

 Hyper Homocysteinaemia: What this protein does in body ?? What is the physiology & -Mode of action: - Homocysteine causes transfer of activated methyl group from tetra-hydrofolate to S-adenyl-methionine. (It therefore plays a significant role in the synthesis of cyteine from methionine. In this pathway there is therefore production of Homocyteine thiolactone. In hyperhomocyteimia there can be abnormal rise of plasma / urinary Homocyteine.

What are the definite & presumptive causes of abnormal rise of Homocyteine: There is considerable ethnic variation on HHcst. Therefore there are -genetic, inflammatory, demographic, ethnic, nutritional, or most importantly an effect of metabolic disorders.

3) What is normal level? Normally the serum level should be less than 10 mmol/L but preferably at about 5 mmol/L.

5) What are the ill effects? Homocyteine, its high level can lead to 1) arterial endothelial more preferentially damage first documented plasma lipopopotein alpha-A, -à then thrombosis & Atherosclerosis. Mild elevation can lead to premature vascular diseases, diastolic dysfunction which is a surrogate marker of early marker of diastolic dysfunction.

2) What about in PCOS, particularly young PCO ?? In young PCOS with hyperhomocyteimia- there be associated rise of uric acid, plasma insulin. Atherosclerosis.

4) Formation of IR. à But regular physical exercise can minimize the IR & WHR.

5) In young PCOS there is significant correlation with Hhcy & WHP(Waist Hip Ratio) .

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Diabetes prevention strategies in India nad abroad

 

 

Prevention of T2D  Is it a still a myth ?? :

In Indian study it was revealed that  behavior modification  can slow the progression toT2D but can’t prevent the DM .Not only Lifestyle but  metformin independently reduced progression of IGT toT2DM but can’t prevent its onset.

The diabetes pre­vention trials, in general, involved intensive individualized interventions. Translational of such research has shown that less expensive, group based lifestyle interventions are also effec­tive in achieving weight loss, thereby reducing risk of T2D.

Prevention of T2D is undoubtedly cost effective. Several large clinical trials have demonstrated that T2D can be delayed or prevented by lifestyle intervention or medications. Most of these studies involved subjects with impaired glucose tolerance (1GT). Almost 40-50 % of those with IGT progress to T2D during their lifetime. Firstly, one should change her/ his Lifestyle Intervention

One of the earliest trials, Study 1:-The Da Qing study in China, demon­strated reduction in risk of T2D with diet, exercise or both, risk reduction by 31-46 %.

Study 2:-  The Finnish Diabetes Prevention Study (DPS) showed a risk reduction of 58 % at 4 years in the intervention group compared to controls. It involved 522 subjects and the interven­tion targeted at five goals; (1) modest weight loss of 5 %, (2) decrease fat intake to <30 %, (3) decrease saturated fat to <10 %, (4) increase fiber and (v), moderate physical activity of at least 30 min per day. Furthermore, the DPS demonstrated that the reduced risk  was proportional to the number of lifestyle goals obtained.’

 

 Study 3  :-The  Diabetes Prevention Program (DPP)one of the   largest randomized control trials, studied 3,234 American multiethnic obese subjects with IGT with a median follow-up of 2.8 years. It showed similar risk reduction of 58 % with intensive life style as in DPS. It has to be noted that in all the above trials, (the benefit persisted for several years after cessation of active intervention.

 

 Study 4:- The Indian Diabetes Prevention Program (IDPP) also showed that lifestyle and metformin independently reduced progression of IGT toT2 Dm though the above trials have proven that behavior modification  can slow the progression toT2D. The intensive personal contact methods used by them may not be universally adaptable due to inadequate resources. Reassuringly,

a recent study in India has demonstrated that less expensive methods like mobile phone messaging can be successfully used to reduce the risk ofT2D. The IDPP showed that metformin was also effective in a lower dose of 500 mg/day in reducing the progression toT2D in Asian Indians. ;

 

 

Study 5 :-In this randomized controlled trial, lifestyle advice through regular text messaging was acceptable to the participants and reduced the risk of progression to T2D by 36 % over 2 years. As the study was conducted on working men with impaired glucose tolerance in an urban population, it remains to be seen if it is acceptable and effective in other popu­lations. However it is an exciting prospect considering the rapid increase in mobile phone ownership, particularly in developing countries with poor health care infrastructure where the impact can be substantial.

Medications for overt DM:- No medication is licensed for use in, those people at high risk of diabetes.

Medications used in treatment of T2D and obesity have also been found useful in prevention, although all have significant side effects. Since not all people who are at risk of diabetes will develop diabetes it therefore becomes important to con­sider the risk-benefit ratio. Currently, in the UK and many' countries across the world, no medication is licensed for use in, those people at high risk of diabetes.

Study 6 : Metformin at a dose of 1,700 mg/day was effective in DPP with 31 % risk reduction and the benefit was more pro­nounced in younger, more obese subjects and in women with prior gestational diabetes.) :-The IDPP showed that metformin was also effective in a lower dose of 500 mg/day in reducing the progression toT2D in Asian Indians. ;

Thiazolidinediones (Troglitazone, rosiglitazone and piogli- tazone) have proven very effective with a 50-70 % reduction m IGT conversion to diabetes in various trials, as has acarbose. though adverse effects are common.

 

What about orlistat ??  Orlistat in combi­nation of lifestyle changes reduced the progression to diabetes by 52 % when compared to lifestyle and placebo; however this drug was poorly tolerated by the participants.

What about Incretin based therapies (GLP-1 agonists and DPP-4 inhibitors) as a mode of prevention/ deferring DM??  Their role in prevention of T2D remains largely to be explored). Such drugs are being increasingly used for their beneficial effects on weight and glycemic control in T2D, but their role in prevention of T2D

remains largely to be  explored).

 

 Liraglutide has been shown to achieve significant weight loss and reduction in prevalence of prediabetes in obese subjects. Nonetheless, there are also cur­rent safety concerns with the use of these drugs in people with established disease

Bariatric Surgery

Several studies have shown benefit of bariatric surgery in resolution ofT2D and arresting progression toT2D in obese subjects. The Swedish Obese Subjects (SOS) study demon­strated a reduction in risk of developing T2D of 75 % at 10-year follow up in the surgical group. In practice, bariatric surgery is recommended in selected subjects with obesity and co-morbidities including conditions like T2D but not for pre­vention of T2D by itself.

Vitamin D

Vitamin D is found to be inversely associated with risk of T2D. A recent meta-analysis of 11 prospective studies found that risk of T2D was 41 % lower for those in top quartile com­pared to bottom quartile of circulating 25-hydroxyvitamin D levels.  The DPP group also demonstrated negative association even with multiple measurements of 2OH -hydroxyvitamin D and adjustment for weight loss/lifestyle/The trials on effects of vitamin D supplementation on risk orT2D have, however, yielded inconsistent results. Though it has been found to reduce insulin resistance, improve beta-cell function and attenuate HbA_|c rise, there is a need for large randomized tri­als with adequate doses of vitamin D over longer periods to establish if supplementation can reduce risk of T2D

 

Take home message

The epidemic of T2D along with growing evidence that it is preventable has triggered international efforts to adapt the

General lifestyle recommendations for prevention of

Obese/overweight men / women. The  aim to lose 5-10 % of body weight initially; continue to lose weight until BMI is in the normal range and maintain weight loss. Physical  activity, as we all know is relevant .Moderate physical activity implies such as walking/ activity cycling/swimming for at least 150 min/week

Increase intake of fibre (wholegrain bread, cereals, lentils

and beans)

Reduce intake of fat and saturated fat will pay a great dividend.

 

Choose fish and lean meat instead of fatty meat Reduce portion sizes particularly if overweight/obese Include fruits and vegetables  

. How helpful is  Screening for T2D and ‘at risk’ population, followed by appropriate intervention ? Ans: Screening for T2D and ‘at risk’ population, followed by appropriate intervention is likely to be cost effective. Individuals with prediabetes (1GT, IFG or an HbA_u. of 5.7-6.4 % according to ADA) should be referred to a support programme aiming for weight loss of 7 %. Dietary modification (total fat. saturated fat and fibre) and modest physical activity (e.g. walking) of 150 min/week.

Metformin may be considered particularly if BMI >35 kg/m², age <60 years and in women with prior GDM although it would be re-assuring to have the evidence base that metformin also reduced the risk of associated cardiovascular disease, from the public health point of view, it is important that the health sector, government and relevant stake holders such as the food industry, develop community-based efforts and national action plans to prevent this growing epidemic of T2D especially in high risk communities.

 still a myth ?? : In Indian study it was revealed that  behavior modification  can slow the progression toT2D but can’t prevent the DM .Not only Lifestyle but  metformin independently reduced progression of IGT toT2DM but can’t prevent its onset. The diabetes pre­vention trials, in general, involved intensive individualized interventions. Translational research has shown that less expensive, group based lifestyle interventions are also effec­tive in achieving weight loss, thereby reducing risk of T2D.

Prevention of T2D is undoubtedly cost effective. Several large clinical trials have demonstrated that T2D can be delayed or prevented by lifestyle intervention or medications. Most of these studies involved subjects with impaired glucose tolerance (1GT). Almost 40-50 % of those with IGT progress to T2D during their lifetime. Firstly, one should change her/ his Lifestyle Intervention

One of the earliest trials, Study 1:-The Da Qing study in China, demon­strated reduction in risk of T2D with diet, exercise or both, risk reduction by 31-46 %. Study 2:-  The Finnish Diabetes Prevention Study (DPS) showed a risk reduction of 58 % at 4 years in the intervention group compared to controls. It involved 522 subjects and the interven­tion targeted at five goals; (1) modest weight loss of 5 %, (2) decrease fat intake to <30 %, (3) decrease saturated fat to <10 %, (4) increase fibre and (v), moderate physical activity of at least 30 min per day. Furthermore, the DPS demonstrated that the reduced risk was proportional to the number of lifestyle goals obtained.’ Study 3  :-The  Diabetes Prevention Program (DPP)one of the   largest randomized control trials, studied 3,234 American multiethnic obese subjects with IGT with a median follow-up of 2.8 years. It showed similar risk reduction of 58 % with intensive life style as in DPS. It has to be noted that in all the above trials, (the benefit persisted for several years after cessation of active intervention.

Study 4:- The Indian Diabetes Prevention Program (IDPP) also showed that lifestyle and metformin independently reduced progression of IGT toT2 Dm though  the above trials have proven that behavior modification  can slow the progression toT2D. the intensive personal contact methods used by them may not be universally adaptable due to inadequate resources. Reassuringly,

a recent study in India has demonstrated that less expensive methods like mobile phone messaging can be successfully used to reduce the risk ofT2D.

Study 5 :-In this randomized controlled trial, lifestyle advice through regular text messaging was acceptable to the participants and reduced the risk of progression to T2D by 36 % over 2 years. As the study was conducted on working men with impaired glucose tolerance in an urban population, it remains to be seen if it is acceptable and effective in other popu­lations. However it is an exciting prospect considering the rapid increase in mobile phone ownership, particularly in developing countries with poor health care infrastructure where the impact can be substantial.

Medications for overt DM:- No medication is licensed for use in, those people at high risk of diabetes.

Medications used in treatment of T2D and obesity have also been found useful in prevention, although all have significant side effects. Since not all people who are at risk of diabetes will develop diabetes it therefore becomes important to con­sider the risk-benefit ratio. Currently, in the UK and many' countries across the world, no medication is licensed for use in, those people at high risk of diabetes.

Study 6 : Metformin at a dose of 1,700 mg/day was effective in DPP with 31 % risk reduction and the benefit was more pro­nounced in younger, more obese subjects and in women with prior gestational diabetes. Study 5(contd) :-The IDPP showed that metformin was also effective in a lower dose of 500 mg/day in reducing the progression toT2D in Asian Indians. ;

Thiazolidinediones (troglitazone, rosiglitazone and piogli- tazone) have proven very effective with a 50-70 % reduction m IGT conversion to diabetes in various trials, as has acarabose. though adverse effects are common.

 

What about orlistat ??  Orlistat in combi­nation of lifestyle changes, reduced the progression to diabetes by 52 % when compared to lifestyle and placebo; however this drug was poorly tolerated by the participants.

What about Incretin based therapies (GLP-1 agonists and DPP-4 inhibitors) as a mode of prevention/ deferring DM??  Their role in prevention of T2D

remains largely to be explored) Such drugs are being increasingly used for their beneficial effects on weight and glycemic control in T2D, but their role in prevention of T2D

remains largely to be explored) Liraglutide has been shown to achieve significant weight loss and reduction in prevalence of prediabetes in obese subjects. Nonetheless, there are also cur­rent safety concerns with the use of these drugs in people with established disease (see Chap. 3).

Bariatric Surgery

Several studies have shown benefit of bariatric surgery in resolution ofT2D and arresting progression toT2D in obese subjects. The Swedish Obese Subjects (SOS) study demon­strated a reduction in risk of developing T2D of 75 % at 10-year follow up in the surgical group. In practice, bariatric surgery is recommended in selected subjects with obesity and co-morbidities including conditions like T2D but not for pre­vention of T2D by itself.

Vitamin D

Vitamin D is found to be inversely associated with risk of T2D. A recent meta-analysis of 11 prospective studies found that risk of T2D was 41 % lower for those in top quartile com­pared to bottom quartile of circulating 25-hydroxyvitamin D levels.  The DPP group also demonstrated negative association even with multiple measurements of 2OH -hydroxyvitamin D and adjustment for weight loss/lifestyle/The trials on effects of vitamin D supplementation on risk orT2D have, however, yielded inconsistent results. Though it has been found to reduce insulin resistance, improve beta-cell function and attenuate HbA_|c rise, there is a need for large randomized tri­als with adequate doses of vitamin D over longer periods to establish if supplementation can reduce risk of T2D

 

Take home message

The epidemic of T2D along with growing evidence that it is preventable has triggered international efforts to adapt the

General lifestyle recommendations for prevention of

Obese/overweight men / women. The  aim to lose 5-10 % of body weight initially; continue to lose weight until BMI is in the normal range and maintain weight loss. Physical  activity, as we all know is relevant .Moderate physical activity implies such as walking/ activity cycling/swimming for at least 150 min/week

Increase intake of fibre (wholegrain bread, cereals, lentils

and beans)

Reduce intake of fat and saturated fat will pay a great dividend.

 

Choose fish and lean meat instead of fatty meat Reduce portion sizes particularly if overweight/obese Include fruits and vegetables   

. Some common lifestyle interventions to reduce progression to T£D are summarized in Table 1.4.

Screening for T2D and ‘at risk’ population, followed by appropriate intervention is likely to be cost effective. Individuals with prediabetes (1GT, IFG or an HbA_u. of 5.7-6.4 % according to ADA) should be referred to a support programme aiming to weight loss of 7 %. dietary modification (total fat. saturated fat and fibre) and modest physical activity (e.g. walking) of 150 min/week. Metformin may be considered particularly if BMI >35 kg/m², age <60 years and in women with prior GDM although it would be re-assuring to have the evidence base that metformin also reduced the risk of associated cardiovascular disease, from the public health point of view, it is important that the health sector, government and relevant stake holders such as the food industry, develop community-based efforts and national action plans to prevent this growing epidemic of T2D especially in high risk communities.

Disease Modifying Drugs or Biological drugs

 What are Biologic drugs?? Ans;

There are some drugs which are termed as “Disease modifying drugs”- abbreviation is “ DMRD “..These drugs are sometimes used in Rh arthritis, Renal Lupus  and modifies Cytokines , Throbaxane -1 etc. Some drugs of this broad family (Biologic Drugs)  are A) TNF alpha antagonists like intercept, Ifiixicam, adalimumab which suppress some reactions in the body including the lung reactions in COVID 19.These group of drugs block the pro inflammatory cytokines and may save the human lungs from severe damage. Assuming that we need urgent shift of Th 1 to Th 2 at alveolus  and protect the lungs tissue against NK cells abrupt rise  at alveolus such kind of  drugs may help..

Contraceptive options: Risks m=,. Efficacy side effects, how long to use, health risk if any. Contraceptives for sick women

 

 

 

 

 

Peoples family planning needs last for entire reproductive lifetime. With increasing age the reproductive intentions change and the couple often changes the contraceptives

How little we know about contraceptives!!!!!
We the doctors of India must be aware of 1) Contraceptive selection(contraceptive choices/ options), available contraceptives 2) myths surrounding the  contraceptives, 3) efficacy of a contraceptive  and contraceptive accidents i.e. failure rate of different contraceptive 4) Pearl index of different commonly used contraceptive 5) What is LARC(Long acting Reversible Contraceptives) .

We as health Care provider must be knowledgeable and regular update our knowledge on -6) contraceptive related health risk of users,7)   Contraceptive  for sick women, 8)  Contraception for teen agers  and elderly women

We also need to brush up our knowledge on   9) Mechanism / Mode of action of a prescribed contraceptive 10) its Side effects: 11) Pre prescription minimal investigations and 12)  measures to minimize side effects. Further we should know 13) When to initiate contraceptive 14) Who are ideal candidates for a given contraceptives and lastly     15) how  long one can take such contraceptive , 16) The interval of follow up with doctor or nurses 17) Noncontraceptive benefits?

At the moment there are about 19 kinds of  contraceptives including two permanent methods . These are 3) COC 4) POP  5)  IUCD   6) LNG-IUS  7) Injectables  8) Implants   9) LAM method of contraception 10)   Other NFP 11)Male condom   12) Female condom  13)  Other vaginal Barrier methods   14) Vasectomy  15) Tubectomy 16) Emergency contraceptives 17) Nuvaring 18) Ortho Evra Patch 19)  Newer contraceptives.

We need to discuss all these with contraceptive seekers as we work in hospitals we must have a thorough knowledge about 19 contraceptives available in India. We should also know how to tackle the minor side effects, brands available in local market, warning signs of a contraceptive, and when to stop specific contraceptives, hormone containg contraceptives in particular.

.

Admittedly, there is dearth of knowledge about the ‘timing of initiation of contraceptives during breastfeeding period’ and also the selection appropriate contraceptive too. To complicate the issue opinions 6n there two issues varies widely because ‘lactation’, ‘nutrition’ and ‘fertility’ are interrelated, and medication of any one may have unforeseen and adverse effects on the others.

Most Indian mothers are unaware about the return of fecundity after childbirth and some are so pragmatic that they believe she will  remain immune to conception so long as breastfeeding is continued. There is another group of more  conservative couple who have negative connotations and unnecessary fear of using hormonal contraceptive in breastfeeding period because they falsely believe that all contraceptives will harm their infant who are breast feeding. This is more true in cases of women with some medical disorders like diabetes, obesity, metabolic syndrome, PCOS, dyslipidaemia , G B stone  smokers ,Women with Past history of Gestational diabetes, Viral hepatitis, ,   hypertension, migraine, epilepsy, ,women with H/O  heart attack, or cerebrovascular accidents,. There are many such unvoiced concerns about the use contraceptives for which many couple do not use effective contraceptive in breastfeeding period.

Similar contraceptive selection for women with uterine diseases like adenomyosis, Myoma, endometriosis, Dermoid , endometriomata, Cancer cervix or CIN genital Kochs abrupt us un a great challenge  on Contraceptive technology. These results in hundred thousands of unwanted pregnancies and many of them are terminated by surgical abortion with all its attendant risks.

Disappointingly annually seven to ten million abortions are carried out in our country and almost one third of children still owe their arrival more to chance than to caring choice. All these speak of culture and poor knowledge on contraceptives for which we doctors are primarily responsible.

Popularizing contraceptive in India comparable to selling a refrigerator to an Eskimo. It requires considerable effort not only by doctors but also by NGO and committee leaders. How many couple you have motivated for dependable reversible contraceptives in the month of August ???

In this deliberations  a threadbare discussion has been made on sequence of resumption of ‘menstruation’ ‘ovulation’ and ‘fertility’ after a childbirth and need for individualization timing of ignition of contraceptives.

It is true that no single method will suit every Indian couple. Most change contraceptive methods a number of times over their reproductive lives. During the breastfeeding period i.e. one month to two years following childbirth clients have options to a range of family planning methods. However, many couple try contraceptive on trial or error basis and can easily find a suitable method which will suit their sex life.

We the gynecologists must try to furnish most up to date in functions about all contraceptives that may be safely used during 1) different ages 2) contraceptive selection for sick women and 3) for breastfeeding without causing harm to infant. It has been described in a edutainment and dumb down process without becoming techno bubble. It is sincerely hoped than on reading this painstakingly prepared treatise the readers will be closer to wisdom filled with scientific information about selection of contraceptives most appropriate for them.

 

 

 

Contraceptive implants

 

Contraceptive Implants

For availability pl enquire Infar(originally Organon)

Overview:

     A contraceptive hormone implant is a device that is surgically implanted beneath the skin. An implant is a small flexible plastic rod which is placed just under skin. It releases progestogen hormone over a number of years. There are two different types of implants. Implanon is a single rod implant and Jadelle contain two rods. These two implants are nowadays commonly used. In china and Indonesia however another implant is used called sino Implant – II.

Implanon is a very small thin plastic rod about the size of a big match stick. It is placed just under the skin of one's inner upper arm. It steadily releases a progestogen hormone called etonogestrel into bloodstream. It works for three years continuously.

     Jadelle is a two rod system implant and contain separate progesterone (levonorgestrel). This exerts contractive efficacy for five years.

     Earlier six rod system was need which was popularly known as Norplant. (Six Capsule implant system). This was effective for five years. These are no longer used as its insertion and removal was difficult and more painful to acceptor. Once inserted into a woman’s arm, the implants do not require any action by the user. Since implants do not  contain estrogen,  require any action by the user. Since implants do not contain estrogen, they do not decrease production of breast milk and thus are suitable for breastfeeding women. They are also a good choice for women who do not want more children but are not ready to opt for sterilization, which is a permanent procedure.

     Subdermal contraceptive implants deliver steroidal progestogens from polymer capsules or rods placed under the skin. The hormone diffuses out slowly over a period of 1-5 years and effectively by passes first-pass liver metabolism. Jadelle (first called Norplant-2) was designed to release the same dose of levonorgestrel but from two rods instead of six capsules. There are three other progestogens in implants currently marketed: e.g. etonogestrel (Implanon); Nestorone (Elcometrine) and nomegestrol acetate (Uniplant, surplant).

Table 1: Different Implants

Six Rods:

Norplant (Levonongestrel) –not used nowadays.

Two Rods:

     Jedelle (levonorgestrel)

     Sinoplant II (Levonorgestrel)

Single Rod:

     Implanon – 3 years (etonogestrel)

     Nestorone – 2years (Nestorone)

     Uniplant – 1 year (nomegestrol acetate)

     Both Norplant and Jadelle one made of contain levonorgestrel as the principal hormone but Norplant was used to be marketed as silastic  capsules while present day Jadelle is marketed as ‘Covered Nods’.

 

Implanon

Overview:

     Implanon is a progestogen only contraceptive implant. It consists of a small plastic rod about the size of a matchstick which is inserted just under the skin on the inside of the upper arm. The rod is very flexible and not likely to be visible. The hormone is released slowly from the device into the bloodstream over 3 years.

     It stops the body from releasing an ovum (egg) every month (this is its primary action). Implanon is a single rod implant manufacture by Organon. The rod contains 68mg of progestin called etonogestrel. It exerts contraceptive efficacy for three years. It is registered in over forty counters but not freely available in India.

 

Mode of Action: Inhibits ovulation

    

     Daily release rate of approximately 30ug etonogestrel/day inhibited ovulation in the majority of women. In order to maintain the required release rate of 30ug etonogestrel/day for a projected duration of use of three years, it was found that an initial release rate of about 60ug/day was necessary. Within eight hours after subdermal insertion, etonogestrel levels are sufficient to maintain contraceptive protection for three years.

 

Implanon though inhibits ovulation but endogenous oestrogen (the main female hormone). Is synthesized normally. Therefore, estrogen deficiency symptoms (dry vagina, hot flashes, loss of libido) do not occur neither there is any adverse effects on bone mineral density. Etonogestrel has shown no estrogenic, anti-inflammatory or mineralocorticoid activity, only weak androgenic and anabolic activity, and strong antiestrogenic activity. None of the implants designed until now exhibits a zero order release, and the amount of steroid released per day drops slowly and progressively throughout the months or years of use. Their effective lives extend from 6 to 84 months and in case of implanon it is three years.

 

Ideal Candidate (Candidacy for implanon):

     Suitable for nearly all women. Nearly all women can use implants, including women should have or have not had children; have just had an abortion, miscarriage are breastfeeding (starting as soon as six weeks after child-birth); have anemia; smoke cigarettes (regardless of age).

     Use of implanon for Nursing-Home:     Lactating women need effective contraception at the time of first menses, after starting supplementary feeding, or at 6 months postpartum, whichever comes first. Some may need it earlier because of personal e.g. minipills, quarterly shots and reasons. Contraceptives for nursing women should not affect lactation and should be effective and safe in the evolving physiological and fertility circumstances associated with breastfeeding. It is often considered that non-hormonal methods do not interfere with breastfeeding infant growth and health and should be considered the first choice for lactating women, but they are less effective.

Fecundity : The rate of conception in human females per cycle

 

Q.1: What is the fertile period during  the entire  spell of menstrual   cycle. ?

The number   of fertile   days of a menstrual cycle is difficult to quantify. The sperms remain alive in the female genital   tract and are   capable     of fertilization for up to 5 days   after ejaculation. The egg appears to be capable of being fertilized for only about 24 hours .

In a recent study   amongst couples   actively trying to conceive   with hormone measurement   to determine the timing of ovulation it was learnt that the fertile   period lasted about six days ending on the day  of ovulation . However in a   woman with reasonably regular   menstrual cycle of about 28 day, day 10   to day 17  is considered   as fertile period . But  in women with irregular   period concluded that   fertile  period should be considered as day  7 to day   15 of menstrual cycle.

Q.2: What is the probability of conception   after one or multiple    acts of intercourse?

Ans:-The probability of  conception after single  act of intercourse is approximately 8%  conception rate has been calculated to be about  but if multiple acts it comes to 13%  per cycle    if intercourse occurs on average  every other    day . But  if it   occurs    only once  a week  the risk of  pregnancy is about 15% . Most  women who   have unprotected intercourse   on a single  occasion   therefore will  possibly not conceive.

Q.3: What is the risk of conception if there is only single act of coitus  in the entire cycle ( expected cycle -  day specific conception   rate i.e. Barrett  and Marshall study )?

Ans: The overall risk of pregnancy after a single act of unprotected   sex on any day of the cycle in 2-4%    and is highest in the days before and just after  ovulation  . There is no day of the menstrual cycles when there   can be certainly   that unprotected   sex would not result in   pregnancy although   the probability is negligible in the first 3 days of the cycle . Timing   of sexual    intercourse   in relation to ovulation   - effects   on the probability of conception   , survival of   the pregnancy    and sex of the baby , (Source : New   England    Journal   of medicine  Vol.333. )

Q. 4 .What is meant by fecundity?? Ans: A normal   fertile sexually active couple not using   contraception   has maximum monthly chance of conceiving    20-25%   .

Q.5 :  What is the spontaneous unavoidable loss of a fertilized zygote?? Will all fertilized human egg give birth to a live  baby ? What is the incidence   of post   fertilization preimplantation   wastage?

Ans: After  fertilization 25% of zygotes  do not  implant   and those  that implant a proportion   is lost before   a pregnancy  becomes  clinically  recognizable Thus  in 42%  cases no clinically recognizable   pregnancy results  even after  fertilization .Eight   per cent   of all clinically recognized  pregnancies are spontaneously lost even if  such cases had demonstrated gestational SAC in TVS.  .

Q.6: Then what is the exact relevance of emergency contraceptives?? Accordingly  prospect of EC within 120 hours  of intercourse  by interruption of the natural development of a fertilized ovum appears very low   and more so after a single  act of unprotected  intercourse. Therefore   in a vast   majority of cases EC addresses a theoretical or statistical   rather   than   an actual chance of   fertilization having occurred  and  lives  the women ‘s    apprehension of  unwanted    pregnancy  considerably.

Q.7: What is the Longevity of sperms ?

There is great individual variation between men and between individual sperm with the same men’s   ejaculate.

Q.  8: What is the rate of spermatogenesis ?? Scientists have shown that – sperm   counts and quality of sperm have  lowered in the recent   years. In normal   healthy men  spermatogenesis    occurs at the  rate 1,000 sperm   per second  from each   testis   and an ejaculate   of   3-5  usually  contains  350   million  sperms  though only one ova  need to be  fertilized. Sperms can remain   alive in cervical    mucus for   5-6  days depend on quality of cervical  mucus.

Q. 9: Frequency   of sexual intercourse  &  knowledge of fertile  period ?

WHO   in the early 1990 estimated that intercourse  takes place   over 42,000 million  times per years. This   means every second there 1,300 ejaculations with possible pregnancy  .Now with increase of population it seems that this may somewhere 2000 ejaculation in vagina per second with possible pregancy  . Different studies   have shown that sperm   can remain alive in female   genital    tract for about six days

Q.10: What is  Safe   period   in human   menstrual cycle? Ans:   Safe   period   in human   menstrual cycle has long    been debated. The whole   of the second week of 4 week long menstrual cycle is potentially fertile i.e.  days 7 to day 14 of cycle. Even sex during   menstruation    can lead   to conception  if by chance   ovulation   occurs on day 7 of cycle , though   this is rare but not  impossible  because sperm  can remain   alive for 5-6 days .

Q.11. What is  abortion rate ?

Abortion rate is defined as the number    of all types of abortions, per 1000  women   of childbearing  age. But    abortion ratio   is calculated  by dividing the number  of  abortions  performed   during a particular time   period  by the number   of live  births  over the  same  period.

Q. 12: What  is General Fertility Rate(GFR) ?

It is   the number of live   births per 1000 women in the  reproductive   age group  in a given years.

transvaginal pulsed Color Doppler in ART programme--how useful in estimating PI,RI, PSV of Ovarian vessels ??

 

 

How useful is transvaginal pulsed   Color Doppler in ART programme??

 

An experienced sonologist can interpret about  i. e 1) Oocyte maturity 2)  the predictability of the number and  3) quality  of the oocytes   and 4) assessment    of the  most appropriate timing  of the administration of human   chorionic   gonadotropin  in cases of assisted  conception by interpreting  the Pulse colour Doppler !!!!

Part I:  How useful is transvaginal pulsed   Color Doppler   One need the combination   of real time   ultrasound pulsed Doppler   and color flow mapping in studying the female   reproductive system on an anatomic and physiological   basis  . Only then it will be successfully possible to assess the hemodynamic changes in various physiological   and pathological   entities in uterus, ovaries and endometrium in particular.

 In fact in many centers the costs of endocrine assessment in the middle part   of ART cycle have been minimized thereby avoiding -repeated venepunture!! . 

ART specialist for last three decades were desperately searching for  a non invasive  procedure  that will   improve  precision of the knowledge  of A) oocyte  maturity B) the predictability of the number and C) quality  of the oocytes   and D) assessment    of the most appropriate timing  of the administration of human   chorionic   gonadotropin  in cases of assisted  conception. With the advanced technology of Sonology & its capability to interpret  the vascular changes   that occur  in    the intraovarian milieu using   transvaginal pulsed   Color Doppler   have  improved   their  understanding  of the peripheral   circulatory  conditions  that reflect  the hormonal changes  that occur   during  spontaneous    and induced cycles.

 

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Part II :  Let us refresh our memories on Vascular   supply of the ovaries before we embark upon to interpret  the Doppler changes of ovarian vessels  in an induced cyce?

  What is genital vascular arcade??   Ans: Ovarian arteries are branches of abd aorta with high blood flow though Lt ovarian vein drains into Lt renal vein. The ovary receives its   arterial   vascularity from two sources the A) ovarian artery  and the B) utero  ovarian branch of the uterine artery . These arteries anastomose to form an arch parallel to the ovarian hilus and constitute   the vascular genital arcade. I don’t know how the ovarian function is interfered when on PPH cases the uterine arteries orsay Int iliac arteries are ligated!!!

 

 However, from the ovarian   hilus the arterial branches   penetrate    the stroma and acquire    a tortuous   and helical   pathway   termed the spiral   or helical arteries demonstrating   high resistance to flow. This facilitates the accommodation to changes  in size with development of the  follicle.

  Arterial tone can be assessed by Pulsed Colour Doppler if one have such a machine & clinic provided  sonologist keeps her / his word visits to your clinic at a particular time : That can be done at your clinic!!! Intravascular pressure and diameter profile of the utero-ovarian resistance artery network: Modulation of resistance or changes in artery tone by hormones, Quality of growing oocyte, No of D follicles instead of repeated  endocrine profile..

Blood flow to the ovary varies dramatically in both magnitude and distribution throughout the estrous cycle to meet the hormonal and metabolic demands of the ovarian parenchyma as it cyclically develops and regresses. Several vascular components appear to be critical to vascular regulation of the ovary. As a first step in resolving the role of the resistance arteries and their paired veins in regulating ovarian blood flow and transvascular exchange, researchers have  characterized the architecture and intravascular pressure profile of the utero-ovarian resistance artery network in an in vivo preparation of the ovary of the anesthetized Golden hamster.

 

Researchers have   evaluated  on anesthetized Golden hamster. And investigated estrous cycle-dependent changes in resistance artery tone.

The right ovary and the cranial aspect of the uterus in 26 female hamsters were exposed for microcirculatory observations. Estrous-cycle phase was determined in each animal before experimentation. The utero-ovarian vascular architecture was determined and resistance artery diameters were measured in each animal by video microscopy. Servo-null intravascular pressure measurements were made throughout the uteroovarian arterial network in 11 of the animals. Architectural data showed a complex anastomotic network jointly supplying the uterus and ovary.

 

Resistance arteries showed a high degree of coiling and close opposition to veins, maximizing countercurrent-exchange capabilities.

 Arterial pressure dropped below 60% of systemic arterial pressure before the arteries entered the ovary. Both the ovarian artery and the uterine artery, which jointly feed the ovary, showed cycle day-dependent changes in diameter.

 Arterial diameters were smallest on the day following ovulation, during the brief luteal phase of the hamster. The data show that resistance arteries comprise a critical part of a complex network designed for intimate local communication and control and suggest that these arteries may play an important role in regulating ovarian blood flow in an estrous cycle-specific manner.

Part IV:- If sonologist fails to come then  it is you who have to do it. Here are

tips:-After   visualization of the pelvic   anatomy  by B mode  and color   Doppler   sonography  the color flow of the  ovaries  can be   explored  with Doppler sample   volume   until the typical  spectral   waveform is seen. As the ovarian artery   traverses   the broad   ligament entering the ovary    at an angle   of approximately    90 degrees   to the insinuating vaginal ultrasound   beam, satisfactory    ovarian Doppler signals   are difficult to obtain vaginally.

 However intraovarian vessels   traverse the ovary at varying   angles   of orientation. With the increased blood   supply   to the ovary   containing the corpus    luteum vessels are relatively easily identified with a color   system   at low angles of insinuation. It is additionally difficult   to visualize ovarian vessels because   the color   flow is usually  not  prominent velocity is low  and the resistance   varies according   to the day of the menstrual  cycle.

Nevertheless it should   be emphasized that the information obtained by color   Doppler   sonography is rarely diagnostic by itself. It should also be noted   that blood   flow demonstrated with color    Doppler   images that depends    on flow velocity is   not directly dependent on the   amount of blood flow and the diameter of a vessel.  Therefore    the vascularity seen on a color flow   image does not always    correlate   with that assessed by angiography or dynamic computed topography.

Part VI:-   Doppler studies while performing Foll monitoring  .  Blood flow during the follicular   periovulatory and mid luteal   period  in spontaneous and induced cycles

: The  ovarian blood flow  of an ovulatory   cycle is more or less   at constant level   throughout the follicular     phase    and then  shows a steady  decline  to reach a nadir on  the  approach to   ovulation.  These blood flow    changes are not seen in anovulatory cycles. The blood   flow   changes that occur  before ovulation indicate   the complexity   of changes that involve   angiogenesis  as well as hormonal factors .

 Furthermore   corpus   luteum blood flow  is characterized by low impedance and high flow  pattern that can    easily be detected   One study    measured the resistance  index    of the flow velocity waveforms  of the uterine and the ovarian    arteries during   the menstrual cycle   in 100 infertile  anovulatory   women compared  with 150  fertile  spontaneously    ovulating   women. The    authors recognized that   the RI of the uterine arteries   was around  0.88   until day 13 of a 28 day cycle. Then a significant   decline began    reaching  0.84   at day 16. These  changes did  not occur in anovulatory cycles   in contrast  there was   an increase  in the RI .

 

 However ovarian flow   velocity  differs   somewhat  from the uterine   vasculature    where the  resistance   index is approximately 0.54  until   ovulation  approaches   after which   a decline   begins 2 days   before ovulation and reaches a nadir   at ovulation . Thereafter it   remains   at this  low level  for four more    days and gradually climbs to a level  of 0.50  .Another   study has looked at the intraovarian  blood flow during   the early follicular,  periovulatory and mid luteal   phases in spontaneous and induced ovarian  cycles. The  researchers measured the pulsatility index  in 8 women   with   spontaneous cycles 20 women  undergoing induction of ovulation   with clomiphene citrate  and 11 women undergoing  controlled ovarian  stimulation   for in vitro    fertilization   with gonadotropin releasing hormone  agonists  , stimulation by   human menopausal gonadotropin    and trigger by  human   chorionic gonadotropin .

 

Although    statistically   non significant the intraovarian PI    showed a gradual   decrease   from the early follicular   through eh periovulatory to the mid luteal phase . Intraovarian  blood flow      velocity    wave from  were found in 20. 5 %  of cases at the early  follicular   phase ,  in 56%  of cases   during   the peri ovulatory phase,    and in 85% during the mid luteal  phase.

Intraovarian     blood flow in relation   to ovarian morphology and function during  the periovulatory period In addition  the indices of the blood flow at a given  site within  the leading  follicle have been    monitored by transvaginal  color Doppler  imaging   over the periovulatory period . Researchers have assessed by    intraovarian     blood flow in relation   to ovarian morphology and function during the peri   ovulatory period.

The main outcome measures   were the PI   and the maximum     peak systolic velocity   from vessels    within the dominant follicle the maximum follicular diameters and its correlation with serum FSH , LH,   and progesterone   levels .

POINT VII: What changes happens in blood vessels just prior to ovulation??  Ans: There is    an apparent   A)  increase in the intra follicular blood flow over the periovulatory   period with an insignificant   trend toward B) lower   values for the mean    PI  and a C) significant trend   toward lower   values for the mean  PI and a  D)  significant increase in the peak   systolic velocity.

These changes appeared to follow   the rise in  circulating LH. The increase  in the peak   systolic   velocity and    the relatively constant PI  suggest  a marked  increase in blood flow  at this time during   the ovarian  cycle  and might   herald  impending  ovulation .

Others   have examined the uterine and ovarian perfusion during the peri ovulatory period. The researchers   measured the flow  velocity   of the uterine radial  spiral and ovarian arteries during  the peri ovulatory period  in spontaneous   and induced  ovarian cycles .They demonstrated that ovarian  flow   velocity  had a RI of  0.52  on the day   before ovulation in the group   with spontaneous cycles and 0.51  in the group with stimulated cycles . The value for the RI tended to decrease whereas blood velocity tended to increase during the day after  ovulation . A nadir of 0.46  was reached one  day  after ovulation in the group  with spontaneous cycles and of 0.43  in the group   with stimulated    cycles. However there   were no statistically     significant differences in the results between spontaneous   and stimulated cycles.

 

Part : VIII:  Role  of transvaginal pulsed color  Doppler  in assisted conception

In the   in vitro  fertilization embryo   transfer   program : The  oocyte  quality and recovery   the embryo quality   and the   receptivity  of the endometrium are   among  the most important   parameters that determine the success  rate.  Several studies   noted that the perifollicular peak   velocity values increase gradually with the increase in size of the   growing follicles. In addition there is a strong positive    correlation between  the size of the   ovarian follicles and their  peak velocity   which   suggests an increase of blood  flow around developing follicles in the course   of the follicular  phase .

Moreover hCG  plays an  important role in inducing an influx of blood within the follicles.  However  it appears that the resistance  index is not a  useful parameter for characterization  of the  intra follicular flow color   Doppler.

 But the  assessment of folliculogenesis  in IVF- ET   patients  was studied in women  undergoing   hormonal stimulation  for IVF. A highly significant elevation of the peak velocity was observed   especially after hCG   injection. Such    rapid rise of blood velocity   was greater   in the right ovary   than in the left. This may be a cause of more ovulation in Rt side of ovary in unstimukated cycles.

Part IX:  The   role of transvaginal pulsed color Doppler ultrasound in the prediction of th outcome of an   in vitro fertilization program  has been assessed in several     studies. Researchers have followed longitudinally during   stimulated cycles and the PI    and the maximum  peak systolic velocity of  the  intra ovarian and the uterine blood flow   were measured . There   were no detectable changes in Doppler   measurements   affecting  the intra ovarian    blood flow. All flow velocity   wave forms obtained   from intra ovarian   vessels showed a low   resistance    with continuous   end diastolic component . The highest individual PI  value  was less   than 1.1  . It is   suggested  that the plateau seen in the Doppler parameters of  the intra ovarian  blood flow   may be explained by the small  peri follicular vessels in the ovary   that appear to offer minimal resistance to  blood   flow. This   operates   as if they are maximally dilated  and consequently once the optimal   flow conditions are achieved   further changes   in endocrine profile may not be reflected  in the Doppler    parameters   of the ovarian blood flow. Secondly the endocrine   profile in IVF  therapy with  GnRH    a differs from that  in spontaneous cycles . the most   important   feature being the lack of the physiological  LH surge prior to the follicular   aspiration therefore the  cyclic   changes seen in Doppler parameters   taken during  spontaneous   cycles do not necessarily  occur   during the stimulation protocol  used in IVF. Thus the PI and PSV    values of the blood flow  in these   arteries   were much      lower than   those of the uterine  artery. In addition as  a consequence of angiogenesis , the peri follicular   blood   vessels  have a different vessel   wall structure from  that of  uterine   artery. It was   noted that the detection rate of  blood vessels   around  the developing   follicles  was 34%  during  suppression  with GnRH  as compared with   86%  at the time of   follicular   aspiration. The low   detection   rate of the  intra ovarian vascularity  during  the suppression period  shows   a novel  effect of  the pituitary desensitization when ovaries  are in a resting  state with   no folliculogenesis.

The basic    keystone  of the hemodynamic  regulation of the intra  ovarian  blood flow  is the accentuation of the blood  perfusion of the ovaries during hormonal   stimulation . This   augmentation in perfusion   is demonstrated by an increasing   number of vessels around the developing   follicle and the acceleration in the  peak velocity     of the blood flow in the  uterine and  intra ovarian arteries .

Some authors proposed   correlating    the ultrasound derived indexes   of the blood   flow in individual follicles   on the day of but before th administration of hCG  with the subsequent   recovery   of the oocytes and the  production of   Perimplantation embryos . Researchers have collected   data  obtained  from women   undergoing  IVF-ET.

The peak    systolic velocity was higher in follicles that this information may also be used to time the administration of hCG    to achieve the optimum number and quality   for patient     management. However   there was no clear   difference   in either PI   or PSV  values   between   pregnant and   nonpregnant    women making   prediction  of the outcome of  the treatment   not feasible with  Doppler .