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Ailmemts & Remedies

Fragile X Syndrome

Alternative Names: Martin-Bell syndrome; Marker X syndrome

Definition:-
Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited mental retardation in males and a significant cause of mental retardation in females.

Fragile X is a family of genetic conditions, which can impact individuals and families in various ways. These genetic conditions are related in that they are all caused by gene changes in the same gene, called the FMR1 gene.

click to see the picture

Boys are usually more severely affected as they have only one X chromosome (they carry one X and one Y chromosome). Girls have a second X chromosome, which can to some extent make up for problems with the faulty one and so they may have only mild disabilities. They may also be carriers of the condition – that is, they are not affected themselves but can pass the condition on to their children.

However the genetics of fragile X are actually more complicated as some people only have a small change called a premutation in the FMR1 gene. While they don’t usually have problems from this , it makes the gene unstable and can develop into a full mutation when passed on to the next generation.

Fragile X affects about one in 3,600 men and one in 4,000 to 6,000 women of all races and ethnic groups. It shows an X-linked recessive pattern of inheritance and changes in the gene can become more serious as it’s passed from parent to child (especially when it is passed from a woman who carries it to her child).

Some people with a permutation of FMR1 may have no, or minimal, fragile X symptoms. But those with full mutation, where larger changes in the gene exist, demonstrate more severe signs of the condition.

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Despite being carriers, some men aren’t affected (even though they have no normal copy of their X chromosome). But men who have the full mutation are almost always affected.

In women with the full mutation, a third have a below-normal IQ, a third have a borderline-normal IQ and the remaining third have a normal IQ

Fragile X includes:
fragile X syndrome (FXS), the most common cause of inherited mental impairment. This impairment can range from learning disabilities to more severe cognitive or intellectual disabilities. (Sometimes referred to as mental retardation.) FXS is the most common known cause of autism or “autistic-like” behaviors. Symptoms also can include characteristic physical and behavioral features and delays in speech and language development.

fragile X-associated tremor/ataxia syndrome (FXTAS), a condition which affects balance, tremor and memory in some older male gene carriers.

fragile X-associated primary ovarian insufficiency (FXPOI), a problem with ovarian function which can lead to infertility and early menopause in some female gene carriers.

Some gene carriers do not exhibit any of these features. To learn more about carriers click here.

Fragile X can be passed on in a family by individuals who have no apparent signs of this genetic condition. In some families a number of family members appear to be affected, whereas in other families a newly diagnosed individual may be the first family member to exhibit symptoms.

Since 1984, The National Fragile X Foundation (NFXF) has been helping individuals with Fragile X, their families, and the professionals who work with them. As research into Fragile X continues, our understanding of who it affects and how it affects them will grow. The NFXF is committed to: 1) supporting and funding all efforts that will increase awareness, 2) improving education, 3) advancing research toward improved treatments and an ultimate cure, and 4) keeping the Fragile X community always well-informed about the progress of these efforts.

Understanding Fragile X: A short, independent film produced by Image Union at station wttw11 in Chicago. (26 min.)

Symptoms:
The main problem in fragile X is intellectual impairment. This can range from very minor, so that the person has a normal IQ and shows no sign of fragile X, to severe learning difficulties. How badly someone is affected depends on the degree of change in the gene.
Click to see the picture
*Hyperactive behavior
*Large body size
*Large forehead or ears with a prominent jaw
*Large testicles (macro-orchidism) after the beginning of puberty
*Mental retardation
*Tendency to avoid eye contact

Family members who have fewer repeats in the FMR1 gene may not have mental retardation, but may have other problems. Women with less severe changes may have premature menopause or difficulty becoming pregnant. Both men and women may have problems with tremors and poor coordination.

Causes:
Fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X-chromosome. Mutation at that site is found in 1 out of about every 2000 males and 1 out of about every 259 females. (Incidence of the disorder itself is about 1 in every 3600 males and 1 in 4000–6000 females.)

Prominent characteristics of the syndrome incl...
Prominent characteristics of the syndrome include an elongated face, large or protruding ears, and low muscle tone. (Photo credit: Wikipedia)

Click to see pictures

Normally, the FMR1 gene contains between 6–55 (29 in Robbins–Kumar pathology textbooks) repeats of the CGG codon (trinucleotide repeats). In people with the fragile X syndrome, the FMR1 allele has over 230–4000 repeats of this codon.

Expansion of the CGG repeating codon to such a degree results in a methylation of that portion of the DNA, effectively silencing the expression of the FMR1 protein.

This methylation of the FMR1 locus in chromosome band Xq27.3 is believed to result in constriction of the X chromosome which appears ‘fragile’ under the microscope at that point, a phenomenon that gave the syndrome its name.

Mutation of the FMR1 gene leads to the transcriptional silencing of the fragile X-mental retardation protein, FMRP. In normal individuals, FMRP is believed to regulate a substantial population of mRNA: FMRP plays important roles in learning and memory, and also appears to be involved in development of axons, formation of synapses, and the wiring and development of neural circuits

Possible Complications:-
Complications vary depending on the type and severity of symptoms.

*Recurrent infections in children
*Seizure disorder

Transmission:
Fragile X syndrome is an X-linked dominant condition with variable expressivity and possibly reduced penetrance.

Because males normally have only one copy of the X-chromosome, those males with significant trinucleotide expansion at the FMR1 locus are symptomatic. They are intellectually disabled and may show various physical features of the fragile X syndrome.

Females have two X-chromosomes and thus have an increased probability of having a working FMR1 allele. Females carrying one X-chromosome with an expanded FMR1 gene can have some signs and symptoms of the disorder or be normal. Although the extra X-chromosome can serve as a backup, only one X-chromosome is active in each cell due to X-inactivation.

Males with the fragile X cannot transmit it to any of their sons (since males contribute a Y-chromosome, not an X, to their male offspring), but will transmit the premutation to all of their daughters, as males contribute their X to all of their daughters. Males never transmit their full mutation (males with full mutations in their blood have premutations in their sperm), and expansion to full mutations never occurs through paternal transmission.

Females carrying one copy of the fragile X can transmit it to their sons or daughters; in this case each child has a 50% chance of inheriting the fragile X. Sons who receive the fragile X are at high risk of intellectual disability. Daughters who receive the fragile X may appear normal or they may be intellectually disabled, usually to a lesser degree than boys with the syndrome. The transmission of fragile X often increases with each passing generation. This seemingly anomalous pattern of inheritance is referred to as the Sherman paradox.

Diagnosis:
Fragile X syndrome was originally diagnosed by culturing cells in a folate deficient medium and then assessing the cultures for X-chromosome breakage by cytogenetic analysis of the long arm of the X-chromosome. This technique proved unreliable for both diagnosis and carrier testing.

The fragile X abnormality is now directly determined by analysis of the number of CGG repeats and their methylation status using restriction endonuclease digestion and Southern blot analysis.

Not everyone with fragile X syndrome has the same signs and symptoms. Even affected people in the same family don’t show the same symptoms. The signs and symptoms fall into six categories:

*Intelligence and learning
*Physical
*Social and emotional
*Speech and language
*Sensory
*Disorders commonly associated or sharing features with Fragile X

Autism and Fragile X syndrome:
Fragile X syndrome can cause a child to have autism or an Autism Spectrum Disorder (ASD) though not all children with fragile X syndrome have autism or an ASD.

For 2% to 6% of all children diagnosed with autism, the cause is the Fragile X gene mutation. Approximately one-third of all children diagnosed with fragile X syndrome also have some degree of autism. Fragile X syndrome is the most common known single gene cause of autism.

From Dr. Randi Hagerman’s statement to the United States House of Representatives Subcommittee on Health and Environment: “…Fragile X represents a portal through which we hope to view and treat a wide variety of other disorders of brain development and function. All children with autism…should be tested for Fragile X.”

Genetic mouse models of Fragile X syndrome have also been shown to have autistic-like behaviors

Treatment:
As yet there are no specific treatments or a cure for fragile X, but emotional and educational support for children and their families are vital to help them reach their best potential.

Most affected children have delayed speech and language development and specialised help from a speech and language therapist is vital. Behavioural therapy may help children and their families to cope with problems such as hyperactivity and impulsivity, and sometimes medication is tried. Behavioural therapy may also help those children who have problems developing relationships to develop social skills and to cope with stressful situations.

Some children cope in mainstream schools, sometimes with some extra help, while others need to go to a school which can provide for their special educational needs.

Prognosis:
The outcome depends on the extent of intellectual impairment that is present as well as emotional and social skills.

Prevention:-
Genetic counseling may help both existing and prospective parents with a family history of Fragile X syndrome, or a family history of other symptoms such as tremor. Genetic testing can help determine the level of risk in these families.

Research:
Recent studies have focused on a number of critical areas. The role of FMRP’s RNA partners, many of which have now been validated through in vitro assays, is of primary importance. Also being examined is the function the various domains of FMRP, an RNA-binding protein, which is still relatively unknown. One hypothesis is that many symptoms are caused by unchecked activation of mGluR5, a metabotropic glutamate receptor, which was found in a 2007 study to contribute significantly to the pathogenesis of the disease;  this suggests that mGluR5 blockers could be used to treat fragile X syndrome

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/fragilex1.shtml
http://www.fragilex.org/html/what.htm
http://en.wikipedia.org/wiki/Fragile_X_syndrome
http://healthtools.aarp.org/adamcontent/fragile-x-syndrome?CMP=KNC-360I-GOOGLE-HEA&HBX_PK=fragile_x_syndrome&utm_source=Google&utm_medium=cpc&utm_term=fragile%2Bx%2Bsyndrome&utm_campaign=G_Diseases%2Band%2BConditions&360cid=SI_148902589_6495451981_1

http://drugster.info/ail/pathography/635/

http://psychology.wikia.com/wiki/Fragile_X_syndrome

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News on Health & Science

The Common Causes of Female Infertility

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Trying For a Baby?

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What happens when you see your doctor?

See your GP in the first instance, if you have any reason for concern.

Your doctor will want to know about your development as a teenager and your periods. You’ll be asked when they started, how regular they are, whether you’ve ever been pregnant before or whether you’ve ever had a pelvic infection or sexually transmitted infection.

You can use our ovulation calendar to help identify when your most fertile days are.

It’s also important to mention any other illnesses you’ve had and any medication you may be taking.

Your doctor will examine you, including an internal examination, and send you for blood tests to check your blood count and hormone levels.

Your doctor may ask your partner about his development too, check his medical history for problems such as mumps, examine him and give him instructions to collect a semen sample for testing.

You may then be referred to a specialist clinic to a specialist clinic for further tests and advice. This is usually done once you’ve been trying to get pregnant for at least 18 months, but may be sooner if you’re in your mid-30s or older.

What can specialists do?
Once referred to a fertility specialist (a reproductive medicine specialist), the cause of your infertility will be investigated.

The treatment will depend on the cause. It can range from hormone treatments and the use of donor sperm, to assisted conception techniques such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

IVF and ICSI
IVF involves removing eggs from the woman’s ovaries and mixing them with either her partner’s or a donor’s sperm in a laboratory. If the eggs are fertilised successfully, they may then be placed back in the womb……….CLICK & SEE

This is a demanding treatment for the couple and only about one in three women will become pregnant after a single IVF/ICSI cycle. Some of these pregnancies will be lost in the early stages. Many cycles may be required before achieving successful pregnancy, and these treatments are not successful for everyone, no matter how many times they’re attempted.

ICSI is sometimes recommended to couples who’ve had no success with IVF. It involves injecting a single sperm into the egg. If a healthy embryo develops, it’s then placed back in the womb as in IVF………..CLICK & SEE

Access to IVF is limited on the NHS. Guidelines from the National Institute for Health & Clinical Excellence (NICE) say women aged 23 to 39 who have an identified cause of infertility or have had unexplained infertility for at least three years should be entitled to three cycles of IVF.

The Government has suggested that each primary care trust starts by offering couples one cycle, working up to three when possible. Access to NHS treatment varies, however, and it can depend on where you live, and what other local conditions are placed on you, such as your age.

Click For more information of   infertility :

Source
: BBC Health.22nd. July.2010

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News on Health & Science Positive thinking

What You Eat or Drink May Help You Get Pregnant

What goes inside a body may have a significant effect in improving female fertility, suggests a study.
…………………………………Pregnant_woman

Dr. Emma Derbyshire and her team, from Manchester Metropolitan University, has found that controlled diet may enhance the chances of getting a positive pregnancy test, even to the point of being as effective as IVF treatment.

The researchers observed that while intrauterine insemination and ovarian stimulation showed a success rate of 33% in conception, dietary advice was virtually as effective, giving a 32% success rate, reports Times Online.

They suggest that some efforts that may help increase a woman’s chances of becoming pregnant, and delivering a healthy baby.

These included restrictive methods like abstaining from alcohol, cutting down on caffeine levels or switching to decaffeinated versions.

Emphasis was also put on the inclusion of plenty of fruit and vegetables in daily diet, which could help to put off the reproductive years.

Source:
The Times Of India

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Pregnancy & Child birth

In Vitro Fertilization (IVF)

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Definition:
In vitro fertilization (IVF) is a process by which egg cells are fertilized by sperm outside the womb, in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed. The process involves hormonally controlling the ovulatory process, removing ova (eggs) from the woman’s ovaries and letting sperm fertilise them in a fluid medium. The fertilised egg (zygote) is then transferred to the patient’s uterus with the intent to establish a successful pregnancy. The first “test tube baby”, Louise Brown, was born in 1978.

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In vitro fertilization (IVF) is a procedure in which eggs (ova) from a woman’s ovary are removed. They are fertilized with sperm in a laboratory procedure, and then the fertilized egg (embryo) is returned to the woman’s uterus.

The term in vitro, from the [Latin] root meaning within the glass, is used, because early biological experiments involving cultivation of tissues outside the living organism from which they came, were carried out in glass containers such as beakers, test tubes, or petri dishes. Today, the term in vitro is used to refer to any biological procedure that is performed outside the organism it would normally be occurring in, to distinguish it from an in vivo procedure, where the tissue remains inside the living organism within which it is normally found. A colloquial term for babies conceived as the result of IVF, test tube babies, refers to the tube-shaped containers of glass or plastic resin, called test tubes, that are commonly used in chemistry labs and biology labs. However, in vitro fertilisation is usually performed in the shallower containers called Petri dishes. (Petri-dishes may also be made of plastic resins.) However, the IVF method of Autologous Endometrial Coculture is actually performed on organic material, but is yet called in vitro. This is used when parents are having infertility problems or they want to have multiple births.

IVF has been used successfully since 1978, when the first child to be conceived by this method was born in England. Over the past 20 years, thousands of couples have used this method of ART or similar procedures to conceive.

Other types of assisted reproductive technologies might be used to achieve pregnancy. A procedure called intracytoplasmic sperm injection (ICSI) uses a manipulation technique that must be performed using a microscope to inject a single sperm into each egg. The fertilized eggs can then be returned to the uterus as in IVF. In gamete intrafallopian tube transfer (GIFT) the eggs and sperm are mixed in a narrow tube and then deposited in the fallopian tube, where fertilization normally takes place. Another variation on IVF is zygote intrafallopian tube transfer (ZIFT). As in IVF, the fertilization of the eggs occurs in a laboratory dish. And, similar to GIFT, the embryos are placed in the fallopian tube (rather than the uterus as with IVF).

Purpose
IVF is one of several assisted reproductive techniques (ART) used to help infertile couples to conceive a child. If after one year of having sexual intercourse without the use of birth control a woman is unable to get pregnant, infertility is suspected. Some of the reasons for infertility are damaged or blocked fallopian tubes, hormonal imbalance, or endometriosis in the woman. In the man, low sperm count or poor quality sperm can cause infertility.

IVF is one of several possible methods to increase the chances for an infertile couple to become pregnant. Its use depends on the reason for infertility. IVF may be an option if there is a blockage in the fallopian tube or endometriosis in the woman, or low sperm count or poor quality sperm in the man. There are other possible treatments for these conditions, such as surgery for blocked tubes or endometriosis, which may be attempted before IVF.

IVF will not work for a woman who is incapable of ovulating or with a man who is not able to produce at least a few healthy sperm.

Diagnosis/Preparation

Once a woman is determined to be a good candidate for in vitro fertilization, she will generally be given fertility drugs to stimulate ovulation and the development of multiple eggs. These drugs may include gonadotropin-releasing hormone agonists (GnRHa), Pergonal, Clomid, or human chorionic gonadotropin (hcg). The maturation of the eggs is then monitored with ultrasound tests and frequent blood tests. If enough eggs mature, a physician will perform the procedure to remove them. The woman may be given a sedative prior to the procedure. A local anesthetic agent may also be used to reduce discomfort during the procedure.

The screening procedures and treatments for infertility can become a long, expensive, and, sometimes, disappointing process. Each IVF attempt takes at least an entire menstrual cycle and can cost $5,000–10,000, which may or may not be covered by health insurance. The anxiety of dealing with infertility can challenge both individuals and their relationship. The added stress and expense of multiple clinic visits, testing, treatments, and surgical procedures can become overwhelming. Couples may want to receive counseling and support through the process.

Aftercare
After the IVF procedure is performed, the woman can resume normal activities. A pregnancy test can be done approximately 12–14 days after the procedure to determine if it was successful.

Risks Factors and Complications
The risks associated with in vitro fertilization include the possibility of multiple pregnancy (since several embryos may be implanted) and ectopic pregnancy (an embryo that implants in the fallopian tube or in the abdominal cavity outside the uterus). There is a slight risk of ovarian rupture, bleeding, infections, and complications of anesthesia. If the procedure is successful and pregnancy.

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Forin vitrofertilization, hormones are administered to the patient, and then eggs are harvested from her ovaries (A). The eggs are fertilized by sperm donated by the father (B). Once the cells begin to divide, one or more embryos are placed into the woman’s uterus to develop (C). (Illustration by GGS Inc.)

is achieved, the pregnancy carries the same risks as any pregnancy achieved without assisted technology.

The major complication of IVF is the risk of multiple births. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g., England) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. A double blind, randomised study followed IVF pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of < 2500 g.[6] However recent evidence suggest that singleton offspring after IVF is at higher risk for lower birth weight for unknown reasons.

Another risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome.

If the underlying infertility is related to abnormalities in spermatogenesis, it is plausible, but too early to examine that male offspring is at higher risk for sperm abnormalities.

Birth defects
The issue of birth defects has been a controversial topic in IVF. Many studies do not show a significant increase after use of IVF, and some studies suggest higher rates for ICSI, whereas others do not support this finding. In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived with IVF, notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia, and anorectal atresia; the mechanism of causality is unclear.[8]

Japan’s government prohibited the use of in vitro fertilisation procedures for couples in which both partners are infected with HIV. Despite the fact that the ethics committees previously allowed the Ogikubo Hospital, located in Tokyo, to use in vitro fertilisation for couples with HIV, the Health, Labour and Welfare Ministry of Japan decided to block the practice. Hideji Hanabusa, the vice president of the Ogikubo Hospital, states that together with his colleagues, he managed to develop a method through which scientists are able to remove the AIDS virus from sperm.

Normal Results:
Success rates vary widely among clinics and among physicians performing the procedure. A couple has about a 10% chance of becoming pregnant each time the procedure is performed. Therefore, the procedure may have to be repeated more than once to achieve pregnancy.

Abnormal results include ectopic or multiple pregnancy that may abort spontaneously or that may require termination if the health of the mother is at risk.

Morbidity and Mortality Rates:
The most common cause of morbidity is ecotopic pregnancy. Pain is associated with most components of the procedure. Mortality as a result of IVF is extremely rare.

Alternatives
Other types of assisted reproductive technologies might be used to achieve pregnancy. A procedure called intracytoplasmic sperm injection (ICSI) utilizes a manipulation technique that must be performed using a microscope to inject a single sperm into each egg. The fertilized eggs can then be returned to the uterus, as in IVF. In gamete intrafallopian tube transfer (GIFT), the eggs and sperm are mixed in a narrow tube, and then deposited in the fallopian tube, where fertilization normally takes place. Another variation on IVF is zygote intrafallopian tube transfer (ZIFT). As in IVF, the fertilization of the eggs occurs in a laboratory dish. And, similar to GIFT, the embryos are placed in the fallopian tube, rather than in the uterus as with IVF

You may click to see->

Intrauterine Insemination (IUI)

Manbir  Online

Digitable Builder

Three-parent embryo formed in lab

Resources:
http://en.wikipedia.org/wiki/In_vitro_fertilisation
http://www.answers.com/topic/in-vitro-fertilisation

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More Sex May Help Damaged Sperm

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For men with fertility problems, some doctors are prescribing a very conventional way to have a baby: more sex.

In a study of 118 Australian men with damaged sperm, doctors found that having sex every day for a week significantly reduced the amount of DNA damage in their patients’ sperm. Previous studies have linked better sperm quality to higher pregnancy rates.

The research was announced Tuesday at a meeting of the European Society of Human Reproduction and Embryology in Amsterdam.

Dr David Greening of Sydney IVF, a private fertility clinic in Australia, and colleagues looked at 118 men who had damaged sperm. Greening and colleagues told the men to have sex every day for a week. After seven days, the doctors found that in 81 percent of the men, there was a 12 percent decrease in the amount of damaged sperm.

Many fertility experts suggest men abstain from sex before their partners have in-vitro fertilization, to try to elevate their sperm counts.

Sperm quality can also be improved if men don’t smoke, drink moderately, exercise, or get more antioxidants.

Since concluding the study, Greening says he now instructs all couples seeking fertility advice to start by having more sex. “Some of the older men look a little concerned,” he said. “But the younger ones seem quite happy about it.”

Experts think sex helps reduce the DNA damage in sperm by getting it out of the body quickly; if sperm is in the body for too long, it has a higher chance of getting damaged.

Some experts said that while Greening’s research is promising, it doesn’t prove that daily sex for men with fertility problems will actually produce more babies.

Greening said he and his colleagues are still analyzing the study data to determine how many women got pregnant.

“Looking at sperm DNA is just one part of the puzzle,” said Bill Ledger, a professor of obstetrics and gynecology at the University of Sheffield, who was not connected to the research. “Maybe this will improve pregnancy rates, but we still need to do more studies.”

Ledger said instructing couples with infertility problems to have more sex could stress their relationship. “This may add even more anxiety and do more harm than good,” he said. He said couples shouldn’t feel pressured to adjust their sex lives just for the sake of having a baby.

Greening said the study’s findings were ultimately very intuitive. “If you want to have a baby, our advice is to do it often.”

Source: The TimersOf India

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