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Even with Diminished Ovarian Reserve You Can Achieve Pregnancy

Even with Diminished Ovarian Reserve You Can Achieve Pregnancy

Even with Diminished Ovarian Reserve You Can Achieve Pregnancy

Diminished Ovarian Reserve: What Does it Means

The number of eggs and their quality are reduced at a given age. Women with diminished ovarian reserve have less eggs and more chromosomally abnormal eggs than women in the same age group. It reflects low response to fertility medications and more difficulty achieving a pregnancy. Women with diminished ovarian reserve may reach menopause one or more years earlier. As few eggs remain, still some of the eggs are chromosomally normal and pregnancy is very possible in women with diminished reserve.

Diminished Ovarian Reserve: How it is Diagnosed

History: Some historical factors may indicate low reserve including cigarette smoking, prior surgery of the ovary (removal of a cyst or an ovary), prior exposure to chemotherapy (particularly cyclophosphamide) or pelvic irradiation, early menopause in other family members (mother, sister), recurrent early first trimester pregnancy loss (indicating low egg quality) and others.

Day 3 FSH: It is an aindirect marker for ovarian reserve. It is produced by the master gland in the brain. levels> 12mIU/mL indicates low reserve. It is less accurate than AMH or ultrasound.

AMH: is a protein produced by the cells surrounding the egg in small size follicles. It is more accurate than day 3 FSH. Levels <1.5ng/mL indicates lowe reserve

Low antral follicle count (Ovarian Reserve)

Low antral follicle count (Ovarian Reserve)

Good antral follicle count (Ovarian Reserve)

Good antral follicle count (Ovarian Reserve)

Vaginal Ultrasound: in expert hands (a reproductive endocrinologist), it is an accurate measure for ovarian reserve. The number of small follicles <10mm especially on day 2-5 of menstrual cycle is an accurate indicator for ovarian reserve and response to fertility medication. The presence of an advanced follicle >13mm on day 2 or 3 is also an indicator for low reserve as it indicates that the ovary is under increased stimulation from FSH produced the master gland.

More details on ovarian reserve tests can be found here.

Diminished Ovarian Reserve: What Should you Do

If all other fertility factors (male factor, tubal factor..) are normal you should attempt to conceive irrespective of ovarian reserve. Ovarian reserve tests are not absolutely accurate. They do predict response to ovarian stimulation but are not very good in predicting pregnancy. Two general options exist: i. regular intercourse or ii. ovarian stimulation to produce more than one egg followed by IUI or IVF.

Diminished Ovarian Reserve: What Should your Reproductive Endocrinologist Do

Your reproductive endocrinologist should ascertain ovarian reserve with multiple modalities: ultrasound and blood work. The infertility workup should be completed first: sperm analysis, hysterosalpingogram test for patency of fallopian tubes as well as preconception labs. Your infertility specialist should be able to advice you on the treatment protocol that is more likely to achieve a pregnancy. Fertility specialist should not deny treatment to women based on diminished ovarian reserve. Every woman with diminished reserve should be offered treatment at least once.

If the treatment plan involves ovarian stimulation, a special stimulation protocol or adjuvant treatment should be considered hopping at increasing the ovarian response (number eggs produced during the cycle). Some of the modifications commonly used are increasing the dose of gonadotropins, use of antagonist or flare antagonist, addition of clomid or letrozole, pretreatment with testosterone and use of growth hormone.

Diminished Ovarian Reserve: What would you expect from fertility treatment

Well it depends on few factors: Age and Relative Response to Fertility Medications

If a younger women e.g <37 years produce two or three good quality embryos at the end of stimulation, they have a reasonable potential to achieve a pregnancy after IVF. The chance of getting pregnant in women older than 40 with few embryos is much lower. When one compare effects of low ovarian reserve and age on reproduction it is clears that age has more negative effect on reproduction than age. Age is associated with low egg quality while ovarian reserve mainly speak for the number of eggs in the ovary. Younger women with low egg production fairs much better than older women with good reserve.

Response to ovarian stimulation is not created equal. Women that produce four or more large follicles >15mm are at much better chance for pregnancy after IVF. On the other hand those that have lesser response <3 follicles are a much lower chance for success and should consider converting their cycle to IUI or just cancel the cycle if they have male or tubal factors. They then can try again after considering a modification of the stimulation protocol. In women that produce > 3 -4 eggs IVF is substantially more successful (about three times) than IUI.

Because the response to fertility medication is difficult to judge just based on ovarian reserve markers, most women should be encouraged to try ovarian stimulation once at least and most women should not be denied treatment based on the notion of low ovarian reserve.

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Androgens: Improving Response to Ovarian Stimulation prior to IVF

Androgens: Improving Response to Ovarian Stimulation prior to IVF

Androgens: Improving Response to Ovarian Stimulation prior to IVF

Ovarian stimulation is the most significant improvement in IVF. Response to stimulation together with age are the most important determinants of successful outcome. Women with prior low response to stimulation and women with expected low response (diminished ovarian reserve) are at higher risk for cycle cancellation and  produce a smaller number of mature eggs and embryos. Many approaches were suggested to improve response in low responders including

Increasing the dose of gonadotropins (injection medications)

Use of antagonist protocol

Use of flare lupron protocol

Use of oral medications  e.g clomid or letrozole

Synchronization of follicles prior to stimulation using estrogens

Minimal stimulation IVF

Adjutant use of growth hormone

Use of androgens.

Androgen may Improve Ovarian response to stimulation

Testosterone is known to increase the sensitivity of the ovary to FSH (the hormone that stimulate recruitment and development of follicles in the ovary). Testosterone increases the number of FSH receptors in the follicle and thus its response to stimulation. Women that naturally have high androgens e.g polycystic ovary syndrome (PCOS) show an strong response to FSH. Androgen stimulation increase growth of early follicles and expand the number of follicles available for stimulation. Agonists (lupron) and antagonists (ganirelex) used in ovarian stimulation suppresses testosterone levels in some women.

Androgen Preparations

Two major preparations are available to deliver androgens prior to starting stimulation

Testosterone gel 10 to 12.5 mg applied to skin per day for 21 days or

DHEA oral tablets 75 mg for variable period 4 weeks to 4 months

Transdermal Testosterone

There were three randomized clinical trials (generally the best type of studies in biological sciences) investigating the use of transdermal testosterone prior to IVF. Of the 221 patients included in these studies. Women receiving testosterone required less fertility medications, had significantly more eggs retrieved and  less cycles were cancelled due to low response. There were no side effects in all studies. There was a two fold increase in pregnancy and live birth rates in women that used transdermal testosterone. There is evidence that transdermal testosterone prior to stimulation improves IVF outcomes.

Oral DHEA

The mechanism of action of DHEA is not well understood. There were many studies on DHEA but only one was randomized clinical trial. When all the studies with control group were considered, they demonstrated a significantly lower number of oocytes retrieved in DHEA treated women when compared to the controls. There was no significant difference in the clinical pregnancy rate between women pre-treated with DHEA compared to those without DHEA pre-treatment.  It is possible that DHEA can improve embryo quality, but this dud not translate into higher pregnancy rate. It is suggested that DHEA should be used for 2-4 months prior to IVF which delays treatment start.

The conclusions related to the use of androgens prior to IVF require more confirmation in larger studies. However, if andregens are used, transdermal testosterone is the preferred androgen pre-treatment prior to ovarian stimulation and IVF.

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Practical Approach to Male Infertility

Practical Approach to Male Infertility

Practical Approach to Male Infertility

Male factor infertility is present in approximately 40% of couples having difficulty to conceive. In most cases, however, it is seldom one factor. A basic element that is encountered in every case is the number and quality of eggs. Other factors in also include sexual factor and other female factors (e.g blocked fallopian tubes). Hence, evaluation of female factors is integral to evaluation and successful treatment of male factor.

Evaluation of female factors includes testing for ovarian reserve and testing of the fallopian tubes for patency. In addition to evaluation of medical, obstetric and genetic risks of getting pregnant.

Evaluation of Male Factor

Reproductive ability in males is initially evaluated through i. Detailed history of male partner and ii. sperm analysis. History can indicate many factors that may reduce the ability to conceive: social habits, erectile dysfunction, childhood infections (mumps), medical disorders, genetic diseases (chromosomal abnormalities, specific genetic diseases as cystic fibrosis), occupational exposure..etc. Unfortunately  in the majority of cases history may not predict abnormalities in male factor

Sperm Analysis

Accurate interpretation of sperm analysis (volume, concentration,  movement and shape) is the most important step in evaluation. It is important to take in consideration each factor separately and then in combination. Normal parameters are volume >2mL, concentration 15million/mL, motility 40% and normal shape 4% using strict morphological criteria (Kruger).

Repeat sperm analysis is commonly recommended when abnormalities are detected. There is no strong evidence to repeating the sperm analysis. If the sperm analysis is to be repeated this should be done at least 2 months later as it would take that long for new sperm to be ‘manufactured’.

Generally 10 million moving sperm sperm per ejaculate (volume x concentration x % motility) is required for successful reproduction with intercourse and IUI. Approximately 2 million motile sperm are adequate for IVF. Lower parameters especially if low morphology <2% require IVF with intracytoplasmic sperm morphology (ICSI).

Other Tests

Genetic screening for chromosome analysis and Y chromosome micro-deletion is required in low sperm concentration (<10 million /mL) and azospermia is required. Abnormalities are found in 5-10% of men and can be transmitted to children. Genetic screening for cystic fibrosis and its congenital absence of the vas deferens is also required if azosprmia (obstructive) is present.

Other sperm tests as pH, fructose and sometimes hormone analysis are sometimes helpful.

Tests for sperm DNA fragmentation is still being evaluated but are not part of routine fertility workup.

Treatment of Male factor Infertility

Improvement in sperm analysis is not the main aim of treatment. The main aim is conception and delivery of a healthy child. Sperm analysis improvement is a surrogate outcome not a final goal. In most cases, the improvement in sperm parameters (count, movement and shape) does not translate into a higher chance for conception. In addition, in the majority of cases there is no specific cause identified for male factor abnormalities. The two practical strategies left are to wait (within what is allowed by female ovarian reserve) for sperm analysis to improve and conception to occur or to use the small / abnormal sperm available for assisted reproduction (ICSI) which is a very efficient strategy.

Four Important Considerations before Treating Male Infertility

a. Female age and ovarian reserve: any treatment for male factor should be guided with the number of eggs in the ovary and their quality (age related). In women with women with low egg reserve and 35 or older consideration to ovarian stimulation (to increase mature egg production) followed by IUI or ICSI should be exercised.

b. Sperm Freezing: In men with moderate to severe male factor one should consider freezing one or more sperm samples. The future sperm parameters cannot be predicted and can deteriorate even to a complete absence of sperm in ejaculates. Sperm freezing is cheep, non invasive and can save men from the need for surgical retrieval of sperm. Men undergoing vasectomy can also consider sperm freezing, prior to procedure,  in case they decide to father children in the future

c. Genetic screening: there are two main values to screening males with moderate to severe sperm abnormalities to chromosomes, Y micro-deletion and cystic fibrosis. To avoid transmission to children and to counsel the couple about the chance of successful surgical sperm retrieval (TESE). In some cases the chance for finding sperm is extremely low that TESE is not indicated.

b. Urological consultation: After female and initial male evaluation is complete, evaluation by a male urologist is very useful. A urologist well versed in male infertility can counsel the couple about the chance for success of surgical sperm retrieval and following correct of obstruction.

Four Treatment Options to Consider

Surgical sperm retrieval: in obstructive and non-obstructive azospermia sperm can be retrieved directly from the testes by a male urologist. Micro-TESE involves dissecting one or both testes and obtaining multiple tiny biopsies from many areas. In real time each biopsy is examined under a microscope. The process is repeated till sperm are obtained. The best chance

Surgical treatment for obstructive azospermia: in men that underwent vasectomy before vasectomy reversal can, if successful, restore fertility. Other areas of obstruction can also be restored by urological surgery.

IUI: in few cases of mild male infertility (producing close to 10 million motile sperm) or mild shape abnormalities, ovarian stimulation and IUI is an aoption for 3 cycles. IUI using donor sperm is also an option.

IVF-ICSI: assisted reproductive technology is very robust and can address the majority of male infertility: low sperm count, low motility, abnormal sperm shape, prior fertilization failure. Its is very efficient that it can achieve a conception with very few available fresh or frozen sperm. It can be synchronized with surgical sperm retrieval so that fresh sperm are used for ICSI. Once sperm are available, the success of IVF is dependent on female age and ovarian reserve.

Interventions to Avoid or Consider Cautiously

Surgical treatment of varicocele: Varicocele is a common finding in infertile males and can be associated with low concentration and motility and higher abnormal shape of sperm. Varicocele surgery does improve sperm parameters. The problem with varicocele surgery is that it is not proven to increase the odds of delivering a child by female partner. Varicocele surgery should be cautiously considered due to lack of solid evidence of its benefits.

Medical treatment: The use of medications (e.g clomid, nolvadex, anastrozole) should be avoided as there is no evidence that they will improve the chance of pregnancy and improvement in sperm parameters. The use of injection medications should only be employed in men with a specific indications related to deficiency of such hormones

Supplements: so far there is NO supplement or ‘vitamin’ proven to increase the chance for successful reproduction in male with sperm abnormalities.

A practical approach to male infertility requires initial evaluation of sperm analysis, ovarian reserve and genetic risk factors followed by a treatment plan oriented with the ultimate goal: conceiving healthy child not intermediate issues as cause of male infertility and improving sperm analysis.

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Frozen Embryo Transfer Vs Fresh Embryo Transfer after IVF

Frozen Embryo Transfer Vs Fresh Embryo Transfer after IVF

Frozen Embryo Transfer Vs Fresh Embryo Transfer after IVF

After embryos are created with in vitro fertilization, should you have your embryos transfer 3 to 5 days later or should embryos be frozen and transferred later in frozen-thaw cycle (FET)? This question became viable after improvement in freezing technology (vitrification) to the extent that the vast majority of embryos (>95%) frozen in The US survive thaw and has high implantation potential.

There are indications to freeze all embryos after IVF i. avoiding ovarian hyperstimulation syndrome,ii. unfavorable uterine lining (thin, fluid..) iii. allow more time for PGD / PGS, iv.personal reasons related to patients.

The aim here is to discuss the merits for and against elective embryo freezing to transfer the embryo or embryos in a thaw cycle. A thaw cycle involves preparation of the uterine lining, embryo thaw and embryo transfer (no stimulation or egg retrieval). Preparation of the lining of the uterus can be accomplished through one of two main methods

a. Natural Cycle FET  :  Natural ovulation is monitored using ultrasound and blood work. The time of ovulation need to be accurately defined. Embryos are thawed 3 or 5 days later and transferred. It requires minimal medications but require regular ovulation.

b. Synthetic Cycle FET  :  Estrogen is administered (patches, pills..etc) till the lining of the uterus reach the desired thickness and pattern. Progesterone is then administered (injections, vaginal tablets) and embryos are thawed and transferred few days later. It does not require ovulation and allows more flexibility in timing of embryo transfer.

There is some evidence that both methods are equivalent with regards to implantation and pregnancy.

On The Advantages of Elective Frozen Embryo transfer

Fresh embryos vs Frozen Embryos

Fresh embryos vs Frozen Embryos

In the US frozen cycles result in equivalent number of pregnancies and deliveries as fresh embryos.

Should Elective Frozen Embryo Transfer be Recommended to The General Fertility Population Undergoing IVF?

In other words, do we have enough data to recommend freezing all embryos created after IVF and transfer later?

The possible advantages cited for performing frozen embryos transfer originates from two sources

1. Physiological information: excessive exposure of the lining of the uterus to estrogen may lead to abnormal development of the placenta and

2. Observational studies: when compared to fresh embryo transfer, pregnancies resulting from frozen transfer are less affected by bleeding and are associated with heavier babies with lower odds for low birth weight.

Conclusions resulting from non controlled studies and physiologic interpretation are not always accurate due to differences between the two groups and cannot be relied upon for definitive conclusions. A definitive study will need to be prospective and patients can be randomly allocated to fresh transfer or elective frozen transfer. This study does not exist at this time

Can Elective Frozen Embryo Transfer Improve Pregnancy & Delivery Rates?

Three studies showed a trend to improve in pregnancy rates following frozen transfer when compared to fresh IVF transfer. The studies should be interpreted with caution as it included young high or normal responders and not low responders and older women. The studies did show an improve in delivery rate, did not track perinatal outcomes and did not include economic analysis of cost and benefits. So a larger and more comprehensive study is still needed.

New Ideas in reproductive medicine, though exciting, still require the scientific rigorous study to ensure that the conclusions are correct and define which group will benefit most from freeze all strategy before its general application to women undergoing IVF.

If you need to freeze your embryos after IVF to avoid ovarian hyperstimulation syndrome, because of unfavorable uterine lining or other reasons, please do so especially if the clinic has a robust freezing program. Freezing of embryos (especially with vitrification) is unlikely to affect your chance to get pregnant. On the other hand if you want to freeze all your embryos to improve your chance of getting pregnant, know that this strategy is debatable and not backed by solid scientific evidence.

When undergoing a frozen transfer cycle and if you have regular ovulation and a favorable lining, consider natural cycle FET over synthetic (medicated) cycle as there is evidence that they are equivalent. Natural cycle avoid external medications and excessive exposure to estrogen

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What is my Chance of Delivering a Baby without Fertility Treatment?

What is my Chance of Delivering a Baby without Fertility Treatment?

What is my Chance of Delivering a Baby without Fertility Treatment?

Women may ask what are my odds of delivering a baby in the next 12 months without any fertility investigation or treatment?

Let me start by saying that a consultation with a reproductive endocrinologist can help you identify any fertility factors unknown to you Moreover, evaluation of  your ovarian reserve can give you an estimate how long can you continue to try. Safety is another aspect of consultation as it can identify medical, obstetric and genetic risk factors to having a baby.

Chance of Spontaneously Pregnancy in One Year (treatment independent)

Ignoring all these aspects, the chance of getting pregnant with intercourse alone, within one year,  is strongly related to age. Data from The American Community Survey (ACS) and National Center for Health Statistics (NSHS) based on study of millions of American women can provide an approximate answer.

If one 100 women living in The US tried to conceive, the odds of giving birth in the coming 12 months based on their age group would be

Age(y)                         ACS (%)                                         NCHS (%)

20–24                             21.5                                                     23.2

25–29                             26.9                                                     28.4

30–34                             26.6                                                    25.6

35–39                              14.5                                                     11.9

40–44                               5.0                                                     2.8

45–50                               2.3                                                      1

ACS American Community Survey 2012.
NCHS National Center for Health Statistics 2013.

 Monthly Fecundity Rate

The odds of getting pregnant and delivering a child each month is a also a function of age.

Monthly Fecundity Rate and age

The Monthly Chance for Conceiving and Delivering a Live Born is Related to Maternal Age

 

 

 

 

 

 

 

 

 

 

 

 

One other aspect to consider is how long have you been trying = how long have been having intercourse with no birth control methods (irrespective of timing of intercourse or any other arrangements). The longer you have been trying with no success, the lower the chance for spontaneous conception.

The chance for spontaneous conception can give women realistic guidance of their odds for spontaneous pregnancy with time and minimize delay in seeking fertility consultation that can be detrimental to future fertility.

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Thyroid Cancer and Future Fertility

Thyroid Cancer and Future Fertility

Radioactive iodine treatment and fertility

Thyroid Cancer and future fertility

Thyroid cancer is diagnosed in 45,000 individuals each year in the US.  Its treatment may affect future fertility in men and women. It is more common in women with female to male ratio of 3 to 1. It is the most rapidly rising cancer in women living in the US. Thyroid cancers are commonly diagnosed in young women in their reproductive years. Treatment of thyroid cancer generally yields excellent results, with the majority of women surviving 10 years or more after diagnosis. Some women develop thyroid cancer due to iodine deficiency in diet or prior neck radiation. Some types of thyroid cancers are related to inheriting an abnormal gene.

Several types of thyroid cancer are recognized 1. Papillary cancer 2. Follicular cancer 3. Medullary cancer 4. Anaplastic cancer 5. Thyroid lymphoma. Papillary and follicular cancers are less invasive tumors and are encountered in the majority of women diagnosed with thyroid cancer. They also respond to estrogen as they carry estrogen receptors. Estrogen may promote growth of thyroid cancer cells. Thyroid cancers are usually suspected on neck examination followed by ultrasound or Iodine scan then biopsy. In general, treatment of thyroid cancer require total thyroidectomy-surgical removal of the thyroid gland followed by radioactive iodine to ablate any thyroid remnants. This is followed by long term thyroid hormone replacement. Long term follow up is required after treatment.

Effect of thyroid cancer treatment on the ovary

Thyroidectomy followed by thyroid hormone replacement is not known to affect future fertility in men and women. Radioactive iodine can affect the number and quality of eggs remaining in the ovary. The effect is dependent on the dose of radioactive iodine and the age at treatment. Twenty to 30% of women experience transient amenorrhea or irregular menses starting about 3 months after treatment. Normal menses resume about 6 months later. Permanent ovarian failure is rare but may occur in women at age 40 or older at the time of treatment. Increased incidence of miscarriage is reported in the first year after treatment. With the exception of miscarriages, there is no evidence that exposure to radioiodine affects the outcome of subsequent pregnancies and health of borne children.

Effects of radioactive iodine treatment on the testes

Effect of radioactive iodine treatment may be more severe in men. and is related to the total dose of radioactive iodine received. Transient reduction in testosterone and sperm count may occur but sometimes permanent reduction in sperm count and testosterone levels. Men who received large total dose sometimes sustain permanent damage to the testes with absence of ejaculated sperm-azospermia. There is no evidence of effects of radioactive iodine on their newborn children, although its advised that men avoid fathering children for 6 months after treatment.

Options for fertility preservation

Men interested in future fertility should consider sperm freezing prior to radioiodine treatment. Women should also consider fertility preservation if they will be treated with radioactive iodine and are older than 35 years. Radioiodine treatment will reduce their ovarian reserve. In addition they will be required to avoid pregnancy for a year or so. Options available for preservation of fertility in women include ovarian stimulation and egg retrieval followed by egg or embryo freezing. Ovarian stimulation can be modified to avoid estrogen exposure during stimulation.  Moreover, in familial thyroid cancers, embryos can be genetically tested to avoid transmission of the abnormal gene to children. Men and women diagnosed with thyroid cancer can benefit from consultation with a fertility preservation specialist prior to treatment to discuss effects on gonads and methods to preserve future fertility. Read more at http://nycivf.org

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Ovarian Reserve Revisited-Do You Have Enough Good Eggs?

Ovarian Reserve Revisited-Do You Have Enough Good Eggs?

Trying to conceive over age 35 is generally not easy

I know because I tried for years to have a baby without success.  While there are many factors which impact conception, one of the first concerns for women over 35 is if they have enough healthy eggs to get pregnant.  Research has shown that women carry a reserve of eggs throughout their lives and that reserve diminishes over time.  There are several tests which help to determine ovarian reserve including antral follicle testing, the clomid challenge and the AMH test which is relatively new.

The antral follicle test

Uses vaginal ultrasound to count and measure the small follicles, antral follicles, on the ovary.  The higher the number of antral follicles, the better ovarian reserve and better odds for conception.

The AMH Test

Anti-mullerian hormone test, measures the levels of AMH in a woman’s blood.  Since this hormone remains relatively constant over the menstrual cycle, it can be tested at any point in the month.  Women with higher AMH levels tend to have a better ovarian reserve and a better chance at conception.

When I decided to try to conceive one last time at age 44

My reproductive endocrinologist began by ordering the Clomid Challenge Test.  For the test, I took clomid, a fertility drug used to induce ovulation, for 5 days.  Generally speaking, the procedure works like this:

  • On Day 3 of your menstrual cycle, a blood test is given to measure your FSH, LH, and estradiol levels.
  • On Day 5 of your cycle, you begin to take a 5-day supply of clomiphene citrate, 100 mg of clomiphene each day for five days.
  • On Day 10, you will have another blood draw to check FSH, LH, and estradiol levels again.

Normal results include low FSH values on both Day 3 and Day 10, and low estradiol values on Day 3.  Results are abnormal if your FSH values are elevated.  Your doctor may decide to re-test if your results are abnormal.

My results were normal but that is a fraction of the total conception story and half of the ovarian reserve story.  Ovarian reserve consists not only of the quantity of eggs but also the quality of eggs.     Research tells us that while tests like the clomid challenge check for the quantity of eggs, the quality of eggs is generally determined better by age.  This is an unfortunate fact for those of us over 35.

According to Dr. James Toner in his paper “Ovarian Reserve, Female Age and the Chance for Successful Pregnancy”, once women reach their mid thirties, specifically 37, their egg quantity begins to diminish at a faster rate.   Tonor also reports that even if egg quantity is good, chances of a viable pregnancy drop due to the diminishing quality of eggs as women age.

Based on the research, it is clear that the averages do not look promising for women over age 35 trying to have a baby.  There is, however, other information to consider.  Let’s take a look at the bell curve.  Basically, about 2/3 of the cases for a given situation fall in the fat part of the curve meaning that averages generally apply to most people.  However, there are still one third of the people who fall outside of the fat part of the bell curve and averages do not generally apply to them.  As you look at your individual situation, it is your lab work, anatomy and physiology that matter.   I am a classic example of defying the odds.  My ovarian reserve quantity was good but that wasn’t what was preventing me from conceiving a child.  It took many more tests to determine that a badly placed uterine tumor was most likely preventing implantation.  At age 44, the research showed that an average woman in my situation had only a 3% chance of having a healthy baby.  Yet, I was able to conceive in two of 4 IUI treatments and gave birth to a healthy little girl 9 months ago at the age of 45.

There are many components to conceiving a child

Ovarian reserve is one of them.  There are also many medical interventions to boost the odds of conception.  Medical research provides us with excellent information about infertility and age including work on ovarian reserve.  While the research tells us that the odds of getting pregnant in late 30’s and 40’s  diminishes, one needs to remember that each woman is unique and she needs to work with her doctor to explore all options in her quest for pregnancy.

Deborah LynnAbout the Author:  Deborah Lynn is the creator/owner of Over 35 New Moms and a former corporate vice president.   She holds degrees in Education, Kinesiology and pursued doctoral study in Physiology.  She spent over 17 years working in the corporate environment and now focuses her time on raising her daughter and helping other women over 35 in their journey to have a baby.  For more information, visit The Resource Guide for Pregnancy over 40 at http://www.selfgrowth.com

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Hepatitis B: what do you need to know if trying to conceive

Hepatitis B: what do you need to know if trying to conceive

Hepatitis B: what do you need to know if trying to conceive

Hepatitis B is relatively common in the US and worldwide. There are approximately one million individuals living in the US with chronic hepatitis B. According to the CDC, the highest rate of infection occurs among those 20 to 49 years old. Approximately 5% to 10% of adults and children older than age 5 with hepatitis B infection go on to develop chronic infection. Globally, 350 million individuals live with chronic hepatitis B infection, according to WHO and other sources. One third of those infected reside in China (乙型肝炎). It is more common in Asia, Saharan Africa and some areas in South America. Migration and medical tourism may increase the magnitude of hepatitis B problem in the US. In Asian countries the prevalence is slightly higher in men and is about 10% of adult population. Universal vaccination of all infants at birth and vaccination of at risk individuals e.g type I and II diabetes, sex partners of hepatitis B infected individuals, men who have sex with men, travelers to high risk areas, can prevent transmission of hepatitis B.

Reproductive endocrinologists and fertility specialists are responsible for detection of hepatitis B in partners and prevent the transmission of hepatitis to non infected partner and newborn. Women and men are tested for hepatitis B at the time of initial fertility consultation. Abnormal results are interpreted and measures are taken to avoid transmission to others, during natural conception and with the use of assisted reproduction (IVF).

Hepatitis B Discordant Couples Discovered Prior to Fertility Treatment

One of the major means of transmission of hepatitis B is sexual intercourse. At initial consultation if one partner is hepatitis B Surface antigen positive (HBsAg) indicating chronic infection, vaccination of the other partner will most likely prevent the transmission of hepatitis B during attempts of natural conception and fertility treatment. The vaccine is administered three times at 0, one month and 6 months. High levels of Hepatitis B surface antibody (anti-HBs) indicates immunity.

During fertility treatment, when the male partner is infected and female partner is not, modification of sperm washing techniques minimize the risk of hepatitis B transmission. These include separation of sperm from seminal fluid and then testing of the sperm for hepatitis B before use IUI or intracytoplasmic sperm injection (ICSI). The use of ICSI may reduce but not eliminate the transmission of hepatitis B virus (controversial).

Prevention of Hepatitis B transmission from Egg Donors

Egg donors are initially screened through careful history to exclude those exposed to risk factors, then a complete physical examination. They are also initially screened for viral infections including hepatitis B. Within one month of egg retrieval, donors are retested using conventional labs as well as DNA based testing for hepatitis B (and hepatitis C and HIV) to further minimize the risk of transmission.

Prevention of Hepatitis B transmission from Sperm Donors

Sperm donors undergo a careful questionnaire related to risk factor, followed by examination and laboratory screening. Sperm is obtained and frozen and quarantined. Donors are then retested using FDA approved laboratories to further minimize the risk of transmission of infectious diseases including hepatitis B.

Prevention of Hepatitis B transmission to Gestational Carriers

Male and female partners (intended parents) are tested in a manner similar to sperm and egg donors. If testing was not possible, the carrier is carefully counseled that FDA mandated testing is not followed. In case of a hepatitis B carrier partner, the carrier is vaccinated prior to transfer of embryos.

Low Temperature Storage of Cells & Tissue from a Hepatitis B infected individual

There were few reported cases of transmission of hapatitis B from frozen tissue. Those cases did not involve sperm, eggs or embryos. As a precaution, reproductive cells from infected individuals are frozen in separate tanks than those not infected. More recently, the use of closed systems that do not allow cells to touch liquid nitrogen in the tank, the use of nitrogen vapor instead of liquid and the sterilization of nitrogen using ultraviolet rays can further minimize the risk of transmission.

Hepatitis B Discovered During Pregnancy

A hepatitis B infected mother have a small risk of transmission of the virus to the fetus during pregnancy. The risk of transmission, however, is significant at the time of delivery.Sometimes medical treatment of mothers is indicated with anti-viral medications to minimize this risk after consultation with a maternal and fetal medicine specialist.

All newborn to a hepatitis B infected mother should receive at birth

i. Hepatitis B immune globulin (HBIG) to neutralize a virus acquired from the mother and ii. Hepatitis B Vaccine to produce long term immunity.

Careful screening of intimate partners, egg and sperm donors can markedly reduce the chance of hepatitis B transmission during natural conception and IVF.

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Ten Reasons why You Should not Use Clomid for Fertility Treatment

Ten Reasons why You Should not Use Clomid for Fertility Treatment

Ten Reasons why You Should not Use Clomid for Fertility Treatment,

Not the Way your Using it Anyway

Ten Reasons why You Should not Use Clomid for Fertility Treatment, Not the Way your Using it Anyway. Clomiphene citrate (clomid) was the first medication introduced for fertility treatment (1960s). It works through masking of estrogen receptors in the brain. The brain, blind to estrogen in the blood, starts pouring FSH, the protein that drives development of dormant follicles in the ovary.

When one considers a fertility treatment: not only the pregnancy and delivery rates per cycle is considered, but also the time to conceive (TTC) and the complication rate especially multiple pregnancy. Clomid is a very attractive medicine to women and gynecologists, alike. It is an oral medication, easy to use for both general gynecologists and women seeking fertility treatment. It is also cheep. It is successful in inducing ovulation in 90% women that do not regularly ovulate e.g. polycystic ovary syndrome. Response to clomid is modest in most cases (1-2 follicles).

In spite of all these advantages, there are many other disadvantages. It, most likely, will not improve the odds of conception in regularly ovulating women. Its indiscriminate use, in The US and worldwide (without ultrasound monitoring of ovarian response), probably makes clomid the drug responsible for multiple pregnancies over all other forms of fertility treatment. Although clomid is successful in inducing ovulation in 80-90% of well selected patients, only 20% become pregnant. This discrepancy happens because of undesirable effects of clomid on the lining of the uterus (thin) and cervical mucus (thick). In my opinion though, many clomid cycles fail due to its in women that are not destined to benefit from it. Those are older and regularly ovulating women with unexplained infertility as opposed to suitable candidates: younger non-ovulating women. Clomid offers little help to women with unexplained infertility (ovulating) because in these women, the majority do not conceive because of chromosomal abnormalities in the eggs. Clomid commonly does not induce superovulation (many follicles) to partially compensate for abnormalities in the eggs.

Do Not Use Clomid Unless

1. Preconception labs are normal. Many patients are prescribed clomid without a complete fertility workup, including genetic screening. If you and your partner are carriers of cystic fibrosis or sickle cell anemia gene abnormalities, for example,you are at risk of transmitting these diseases to your future children (1:4). Genetic screening should be performed BEFORE starting fertility treatment. It does not help you to detect these abnormalities after pregnancy ensues. Decline clomid or any other fertility treatment without proper preconception history and lab tests.

2. Evidence of patent tubes. After ovulation induction, using clomid, the eggs has to be picked up by the fallopian tubes. Sperm also has to enter the fallopian tube to allow fertilization. Completely blocked fallopian tube may prevent the egg and sperm to meet. Partially blocked fallopian tube may allow fertilization but the the embryo may become stuck in the tube leading to ectopic pregnancy.

3. Near normal sperm analysis. A sperm concentration of < 15 million per mL and movement < 50% may reduce the odds for fertilization and reduce the chance of pregnancy after clomid treatment.

4. If you ovulate regularly. Together with normal sperm analysis and open tubes, that indicates you have unexplained infertility. The most likely cause for not conceiving is chromosomal abnormalities in the eggs. We cannot fix chromosomal abnormalities if the egg but we can induce the ovaries to produce more eggs. More mature eggs means more chance of producing a normal egg. Clomid induces the ovary to produce 1-2 eggs in most cycles, thus does not address effectively egg abnormalities. On the other hand, if you are young and do not regularly ovulate, clomid is able to induce ovulation and potentially solve your problem.

5. Without monitoring. Some women are more sensitive to the effects of clomid. They respond by producing a large number of follicles. The safest approach here is to cancel the cycle and restart another treatment with a lower dose. Although the risk of multiple pregnancy with clomid is about 10%, women that respond with producing a large number of follicles are at a much higher risk. Careful monitoring of response, using vaginal ultrasound, is required in all clomid cycles.

6. Use the lowest dose that leads to ovulation (start with one tablet per day). Do not increase the dose if ovulation took place at a lower dose. Most patients get pregnant at adoses of 50 to 150 mg (1-3 tablets) per day. Increasing the dose does not increase the chance for pregnancy and increases the side effects of clomid e.g thin endometrium, chick cervical mucus..

7. Do not use clomid more than 3 months (6 months life time max). The majority of women get pregnant in the first three months of treatment. If you are younger and ovulate on clomid and would like to try few more months, then 6 months is the maximum amount of time you should use clomid in your life time.

8. Clomid less likely to lead to pregnancy  delivery in women >38y. In women 38 or older with unexplained infertility, there is good evidence that clomid-IUI is inferior to IVF. The vast majority of women in that age group that start on clomid end up switching to IVF to achieve pregnancy.

9. Expertise with optimizing clomid cycles: clomid cycles should be supervised by a physician with expertise in clomid dosing, use of repeat courses, use of adjuvant treatments as estradiol and IUI. This enables maximizing the benefits of fertility treatment and tailoring treatment to individual woman.

10. Use letrozole before using clomid. Accumulating evidence from many studies, including randomized clinical trials, indicates that letrozole is superior to clomid in terms of achieving pregnancy. Applying the same principals above, letrozole should be considered as the initial treatment for anovulatory infertility.

On tailoring Fertility Treatment to Specific Patient’s Needs

In too many times, the use of clomid for fertility treatment is a stark example of tailoring patients to treatments familiar to general gynecologists, rather than individualizing fertility treatment to women biology and fertility needs, citing ease of use, perceived safety and familiarity. Cheep treatments that appear safe can quickly become aggressive and unsafe if they lead to low pregnancy rate and high multiple pregnancy. The time lost treating older patients with clomid for a prolonged periods can be detrimental to their ovarian reserve and can minimize the chance for eventually achieving pregnancy and delivery.

On men and clomid

There is no proof that men benefits from the use of clomid and similar treatment to improve sperm parameters. Specifically, there is no evidence that female partners of men that were prescribed clomid conceive at higher rates. With very few exceptions, clomid should not be used to treat male factor infertility.

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Fertility Treatment for Busy Professionals

Fertility Treatment for Busy Professionals

From TTC to a Viable Pregnancy

If you and your partner has been trying to conceive (TTC) and your busy with work commitments, here are few tips that help you save time and shorten the time to conceive. Understanding few basic fertility concepts are helpful. What is fertility? It is the ability to conceive with regular unprotected intercourse. If you are having adequate frequency of intercourse, then you have been trying, irrespective of timing of intercourse. If this goes on for one year, if less than 35 or 6 months if 35 or more, then you are having difficulty getting pregnant.Female age is the most important fertility factor

Percent of currently married, childless women 15-44 years of age who have impaired fecundity by current age (from CDC: The National Survey for Family Growth):

 

2002 2006-2010
   Total 15-44 years    25.3%   21.2%
   15-29 years    17.3%   11.0%
   30-34 years    24.5%   14.2%
   35-39 years    33.9%   39.3%
   40-44 years    42.8%   47.1%

The longer you try, without conceiving, the stronger the indication that you have a significant problem with fertility.

The factors that need to be tested at initial workup include:

i. Ovulation and ovarian reserve

ii. Fallopian tubes: open or not

iii. Male factor: sperm analysis and

iv. General factors related to safety: infectious diseases and genetic carrier screening.

But how do you get all that done, understand the results, decide with your reproductive endocrinologist on a fertility treatment plan and execute the plan promptly, while you hassle your daily work and life engagements? A coordinated effort between you, your fertility specialist and other personnel enables you to promptly understand your fertility potential. A flexible reproductive endocrinologist can grant you an appointment at a time that does not disturb your work schedule. At your initial visit, ultrasound is performed for evaluation of ovarian reserve and any abnormalities in the uterus. In the same day, blood is drawn from you and your partner and can be sent for testing. Also a sperm sample can be submitted in the same day or few days later for sperm analysis. Hysterosalpingogram (HSG) can be performed by your physician or a radiologist within 1-2 weeks. Then, Can you communicate electronically with your physicians? This enable efficient discussion of lab results and subsequent steps.

How Fast Can You Decide on a Fertility Treatment Plan? It depends on many factors related to the complexity of fertility issues uncovered during the workup, need for surgery e.g to remove fibroids, polyps or dilated fallopian tubes, proposed fertility treatment, need for genetic testing of embryos (PGD) and need for third party reproduction (donor eggs, donor sperm, gestational carrier). If complex treatment is required usually a second visit is helpful for evaluation of the uterine cavity, trial transfer, training on fertility medication self administration. Handling of insurance and dispensing fertility pharmacies also help reduce the burden on women busy with work engagements.

Many women are advised to continue to try to conceive naturally (3 to 6 months). For those requiring fertility treatment usually a fertility treatment plan can be executed in 10 to 20 days and within 5 to 8 visits. Again the flexibility of the practice in scheduling and communication allow you to execute  around your daily work and family commitment.

The flexibility of the fertility clinic, efficient planning of visits and use of secure electronic communication methods enables women to go through fertility treatment with minimal inconvenience and work interruption.

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