Fertility Consultation with a Reproductive Endocrinologist

A reproductive endocrinologist is a specialist trained in helping women / couple get pregnant. Careful preparation for fertility consultation and adequate time devoted to the encounter itself can help identifying infertility factors and pointing to the most cost-efficient fertility treatment.

Who should consider fertility consultation?

1. Women or couple not able to conceive after two years (female age <35 years), one year (female age >35 years) or 6 months (female age >40 years) especially after repeated unsuccessful attempts at timed intercourse or simple treatment (e.g clomid)

2. Women with known fertility factor (no ovulation, endometriosis or tubal disease / pelvic scarring, fibroids..)

3. Men with known fertility factor (decrease count, motility or morphology of sperm, difficulty with ejaculation or erection)

4. Women or men who are at risk for reduced fertility due to disease or disease treatment (e.g. cancer, cancer treatment, chemotherapy, lupus, prior surgery, irregular menses or absence of menstruation)

5. Recurrent pregnancy loss in the first or second trimester of pregnancy

6. Women or men known to be carriers of genetic disease, conceived in a baby affected with a genetic disease or with family history of genetic problems (e.g. chromosomal abnormality, sickle cell disease, BRCA carrier..)

7. Other indications: same sex couple, individuals desiring pregnancy through donor sperm or donor oocytes, women desiring fertility extension through social egg freezing

Preparation before fertility consultation

Collect prior medical documents 1. Sperm analysis 2. Hysterosalpingogram (HSG) report and films if available 3. Lab tests 4. Genetic consultations if any 4. Medical reports from your physician about any significant disease 5. Operative reports of any abdominal or pelvic surgery. Allot 1.5 hours for the consultation and write down any questions that come to your mind.

During Consultation

Structured consultation with  a reproductive endocrinologist consumes approximately 60 to 90 minutes. Components of encounter include

1. History: to review information related to ovarian, tubal and male factors of infertility as well as medical, surgical and personal histories. Detailed family and genetic history is essential to identify and possibly test for risk factors of genetic disease in the newborn.

2. Examination including general, abdominal and pelvic examination

3. pelvic ultrasound aiming at detecting abnormalities in the uterus, ovaries and the pelvis. Ultrasound is an excellent tool to estimate ovarian reserve-antral follicle count.

4. Explaining the required tests needed to investigate ovarian reserve, male and tubal factors as well as prenatal tests required of any woman attempting to conceive.

5. Outlining a provisional plan for investigation and treatment of infertility.

All the required tests can be finalized within 2 to 3 weeks, enabling the person or couple to make informed decision about the next step in fertility treatment

 After Consultation

Before making any treatment decisions concentrate on completing the required investigation including sperm analysis, test for tubal patency (HSG) and tests for ovarian reserve. Prenatal tests before attempting to conceive including reproductive hormone assay, infectious disease profile and genetic screening tests should also be obtained.

A second visit or phone call with your reproductive endocrinologists outlining the results of fertility tests is highly advisable. Based on theses tests, treatment plans are finalized.

Five points to consider before starting treatment

1. Time commitment: Fertility treatment may require multiple visits over several months. Its important that visits are tailored around your schedule with minimal time off work.

2. Cost is also an important consideration as well as resources available to help you.

3. Potential undesired outcome especially multiple pregnancy. For example women desiring only a singleton pregnancy should lean towards IVF with single embryo transfer rather ovulation induction with gonadotropin injections.

4. Risk of pregnancy in older women and women with medical disorders

5. Is surgery required before fertility enhancing treatment e.g. removal of polyps or fibroids

If you decide to pursue treatment you need to be advised of the schedule of treatment cycle, type and self administration of medication.

After achieving pregnancy

You should undergo all recquied pregnancy screening including screening for abnormal chromosomes in the fetus, amniocentesis of chorionic villous sampling-CVS even if preimplantation genetic diagnosis-PGD was done on embryos as well as consult with high risk obstetrician if needed.

What Does Borderline Ovarian Tumor Mean to Your Fertility?

Fertility in women diagnosed with borderline ovarian tumors can be reduced or lost due to surgical treatment. Counseling regarding fertility preservation shortly after diagnosis can increase the chance of pregnancy following treatment.

Borderline-low malignant potential ovarian tumorLow malignant potentials

The cells in borderline tumors, proliferate more than benign ovarian cysts but less than frank malignant ovarian tumors. Multiple layers of these cells are seen on pathology slides, but they do not invade surrounding tissues as in malignant tumors. They are diagnosed in approximately4000 of women each year in the US and are more commonly encountered in reproductive age women. These tumors are usually cystic, sometimes with surrounding implants. Low malignant potential tumors are treated surgically (removal of cyst, removal of the ovary or sometimes removal of both ovaries and the uterus). They generally do not require chemotherapy for treatment. The majority of these tumors are associated with very high survival (10 year survival >90% in stage I and II ), although some may recur or turn malignant.

There is no difference in survival if borderline tumors were treated with removal of the cyst, removal of the ovary or removal of the uterus and both ovaries. Recurrence may be lower after hysterectomy (5%) compared to salpingoophorectomy (15%) and cyst excision (30%). The high rate for recurrence after conservative surgery indicates the need for strict and long term follow up (pelvic exams, ultrasound and tumor markers). Some recurrences take place years after initial surgery and are sometimes malignant.

Fertility risks in women diagnosed with borderline tumors

Fertility risks in women diagnosed with low malignant potential ovarian tumors include loss of ovarian tissue and pelvic scarring that can block the fallopian tubes especially if open approach is used for treatment compared to laparoscopy (minimal acess surgery). Some loss of ovarian tissue does occur even during cyst removal from the ovary. Ovarian reserve can be tested after surgery using transvaginal ultrasound evaluation for ovarian volume and number of antral follicles. Ovarian function can also be assessed using day 2 FSH and estradiol levels and antimullerian hormone.

Fertility preservation strategies in women diagnosed with borderline ovarian tumors

1. Conservative surgery

Ovarian cystectomy can be considered in reproductive age women, especially in early disease with favorable pathology and absence of implants. Recurrence is relatively high but can be managed with repeat excision if not malignant. If pregnancy is desired following surgery, fertility factors; ovulation, fallopian tubes and sperm factors should be investigated and treated accordingly

2. Embryo and oocyte cryopreservation

Women at risk for diminished fertility due to surgery, especially if requiring removal of the ovaries or repeat excision of cyst, can consider ovarian stimulation, egg retrieval and egg freezing or  IVF and embryo freezing. There is no evidence that ovarian stimulation and exposure to high estrogen increases the risk for recurrence. It is not clear if border line cells are sensitive to estrogen increase during ovarian stimulation. Two options are available to reduce estrogen exposure: to perform IVF in a natural cycle (low egg yield) or to modify the stimulation protocol, through adding an aromatase inhibitor, similar to that used for breast cancer. Alternatively, short stimulation followed by retrieval of immature eggs followe by in vitro maturation can be performed.

Women diagnosed with borderline ovarian tumors are at risk for diminished fertility because of surgical treatment(s). This is especially true if repeat surgical excision is required. Collaboration between a gynecologic oncologist and a reproductive endocrinologist enable adequate surgical treatment, strict follow up and preservation of future fertility in reproductive age women.

 

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.

About 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.over35newmoms.com

Fertility and Fertility Preservation-Beware of What You Read

Fertility treatment especially assisted reproductive technology-IVF enabled many women to achieve pregnancy even those with the most difficult cases of infertility. Advances include ICSI-injection of a single sperm into an egg ,  PGD-biopsy of embryos and polar bodies for genetic diagnosis, of specific genetic diseases, prolonged culture of embryos to blastocyst stage-day 5 to 7 and TESE-surgical sperm retrieval.

Meanwhile, a new host of fertility treatments emerged in the past 10 or so years that were not thoroughly studied including egg freezing, ovarian tissue freezing and transplantation, IVM-in vitro maturation of oocytes, PGS-preimplantation genetic screening for chromosomal abnormalities in the emryo or oocyte and generation of ‘artificial’ eggs or sperm. These procedures carry great promise to advance reproductive options for men and women and can be tailored to their medical or social circumstances.

Potential issues with new reproductive technologies include efficacy, short and long term risks to the mother and children. The American Society for Reproductive Medicine-ASRM states that “procedures for the diagnosis or treatment of infertility will be considered experimental or investigational until the published medical evidence regarding their risks, benefits and overall safety and efficacy is sufficient to regard them as established medical practice”

Information disseminated about fertility procedures online and in lay press are sometimes inaccurate or convey unrealistic expectations. Recently, a same sex couple curbside me to recommend a physician to harvest one partner bone marrow to produce artificial gametes that can then be used with the other partner gametes. When I explained to them that this experimental and was never accomplished in humans, they were very  dismayed and disappointed, confirming that they read about the procedure  online.

Looking at published studies discussing new reproductive technologies one can infer

Egg freezing

Still considered investigational by the American Society for Reproductive Medicine. Not suitable for all patients based on their ovarian reserve. No large studies comparing the efficiency of egg freezing in comparison to the established technology of embryo freezing. No long term follow up data for children conceived using thawed oocytes.

Ovarian stimulation in estrogen sensitive cancers

Using conventional protocols for ovarian stimulation in breast cancer and other estrogen sensitive cancers was not studied in terms of its effects on cancer recurrence. Using special protocols to reduce estrogen exposure during stimulation was not studied long enough. In short and intermediate terms, however, it does not appear to increase recurrence.

Ovarian Tissue Freezing

This is the most investigational technique for fertility preservation. Ovarian tissue is harvested and frozen for later transplantation. Only sporadic case reports were published. It is considered in women with very high risk for ovarian failure e.g. after chemotherapy. There is also the risk for transmission of malignant cells within the graft at the time of transplantation. The outcomes of children conceived after transplantation is unknown.

In vitro maturation

Immature eggs are not suitable for fertilization with sperm. Immature eggs can be harvested, matured in the lab then fertilized or frozen. ‘Cultivating’ very immature eggs from primordial follicles in the lab is experimental and was not done in humans yet. Immature eggs obtained after short period of ovarian stimulation can produce a viable children.  This procedure is more applicable to women with very good ovarian reserve. The long term safety of the procedure is not known yet.

Pre-implantation genetic screening for aneuploidy

Many eggs in every woman are not chromosomally normal-having an extra or missing chromosome-egg quality. Fertilization of these eggs result in chromosomally abnormal embryos. The majority of abnormal embryos do not implant or are miscarried. Testing of embryos to select the normal ones was suggested as a method to increase the pregnancy rate. This is yet to be proven in a peer-reviewed scientific publication. The exact embryo stage to test and the method of testing are still debated.

Artificial gametes

The concept that eggs and sperm can be generated from human embryonic stem cells was shown in mice. The function of the resulting gametes is unknown. This was never accomplished in humans. If functional gametes can be produced from other cells, likely applying this technology in medicine will require another decade or more.

Beware of what you read

Many new reproductive technologies are available to address one or more medical or social issues related to reproduction. Some of these technologies are experimental, not efficient or their outcomes not studied long enough to ensure its safety. They may be applied in limited or monitored settings e.g research or for those that at risk for loosing their fertility and have no other options. Detailed discussion with woman / couple is essential to ensure that the they have realistic expectations concerning their outcomes and that uncertainty about their safety is clearly explained.

Read more at http://nycivf.org

Fertility Preservation via In Vitro Maturation

Immature oocyteIn vitro maturation of human oocytes can be used for fertility preservation. In vitro maturation-IVM indicates that eggs are retrieved without stimulation or after a short period-about 3 days-of treatment with fertility medication. Oocytes are then either 1. Frozen as immature eggs, 2. Matured in the lab for 24 to 30 hours and then frozen as mature eggs or 3. matured in the lab and fertilized using direct injection of sperm-ICSI and the resulting embryos as frozen. Freezing mature eggs generally yields better outcomes that freezing immature eggs. Vitrification appears to result in better survival than slow freezing of oocytes.

Advantages of in vitro maturation

IVM can be accomplished without prolonged exposure to fertility Mature oocytemedication-3 days versus 14 to 21 days for classic IVF cycles.  Estrogen does not increase to the same levels as seen with IVF, which may be advantageous for some estrogen sensitive cancers as breast cancer. Newer approach to ovarian stimulation using aromatase inhibitors in women diagnosed with breast cancer, enables ovarian stimulation to proceed without marked increase in estrogen levels. Because less fertility medication are used, the cost and the risk for ovarian hyperstimulation syndrome are less than conventional IVF

Disadvantages of in vitro maturation

As a reproductive endocrinologist attempt to retrieve eggs from small immature follicles, he or she is successful in doing so 50% of the time-approximately five eggs are retrieved from 10 follicles. Furthermore, 70 to 80% of those complete maturation in the lab making the process much less efficient than IVF. Very few labs in the world reported consistent success with IVM and only in select patients-those with high ovarian reserve. Research is ongoing to improve our ability to complete maturation of eggs in the lab. The success of this method is however, limited by woman’s ovarian reserve and our ability to retrieve these immature eggs. IVM is more suitable for women with PCOS or large number of small follicles in the ovary.

Safety of in vitro maturation

A relatively small number of babies were borne worldwide using IVM. There are no long term data on the health of children conceived using IVM. Moreover, data on outcomes are very scarce on babies borne after both IVM and egg freezing. One study showed that babies born after IVM are larger than those conceived with IVF and more frequently required cesarean delivery. Long term neurological outcomes are still unknown.

In vitro Maturation of immature oocytes after a conventional IVF cycle can be performed, aiming at increase the egg yield. After stimulation with fertility medication for 10-14 days, eggs are retrieved. Mature eggs are fertilized with sperm and immature eggs are left in culture to mature-instead of discarding them. Immature eggs are left over oocytes and in the experience of many labs seldom produce a good quality embryo or pregnancy.

In select patients with good ovarian reserve, in vitro maturation can be considered after counseling patients that this so far a less efficient approach than IVF and that the long term outcomes of children conceived via IVM is still unknown. Read more at http://nycivf.org

Fertility in Women Diagnosed with Chronic Myeloid Leukemia

Women and men diagnosed with chronic myeloid leukemia  should consider fertility issues and safety of pregnancy while under treatment. Chronic myeloid leukemia (CML) is formed of malignant cells from the bone marrow. It may later spread to the blood stream or other organs. It may also progress to a fast growing stage-acute leukemia. It is diagnosed in 2000 women and 2800 men yearly in The US, mostly during their adult years. Most individuals diagnosed with CML carry an abnormal chromosomal arrangement called Philadelphia chromosome. Many patients do not have any symptoms. CML is suspected from blood counts and confirmed by examining blood smears and bone marrow examination.

Newer drugs like imatinib, dasatinib and nilotinib have changed the treatment of CML dramatically. More than 90% of patients that received these medications survived for 5 years or more. These belong to a group of medications called tyrosine kinase inhibitors (TKIs). These medication slow the propagation of lymphoma cells. Their side effects are less than standard chemotherapy. Response to treatment is assessed using blood counts, the presence of Philadelphia chromosome and molecular genetics tests for a specific gene. Some individuals require stem cell transplantation. Transplantation requires treatment with high dose chemotherapy and total body irradiation, both are associated with very high risk for ovarian failure.

Effects of TKIs on fertility. Animal studies indicate that exposure to TKIs during adult life was not associated with impaired fertility in males and females. Exposure before puberty lead to reduced sperm production in males. There has been few case reports of low sperm count and early ovarian failure after exposure to imatinib in humans. This was not reported in large studies. Because of the possible effects of imatinib on fertility and because all individuals treated for CML are at risk for progressive disease requiring stem cell transplantation, men and women diagnosed with CML should consider fertility preservation. Men should consider sperm freezing. Women should consider embryo cryopreservation (if they have a partner) or egg freezing.

Effects of leukemia on pregnancy. In general pregnancy itself does not  appear to affect the prognosis for leukemia There is no evidence that  brief exposure to imatinib in early pregnancy is associated with adverse outcomes  or abnormalities in the babies. There are no extensive data, however on the effects of imatinib and data on the effects of newer TKIs dasatinib and nilotinib are very sparse. Women are usually advised to use a birth control  method while on these medications. In one study two of  16 babies had minor abnormalities (hypospadias in one baby and rotation of small intestine in one baby) that were surgically repaired. Women who were in remission and chose to stop imatinib during pregnancy, had 40 to 50% chance of showing evidence of propagation of the leukemia cells. The majority of them though achieved remission again after re-starting treatment.

Children born to men who are actively taking imatinib at the time of conception appear healthy and current advice is not to discontinue treatment. This is based on outcomes of 60 pregnancies  reported worldwide in female partners of imatinib-treated men. In contrast the data relating to children born to women exposed to imatinib during pregnancy are less encouraging. Although numbers are small-12 congenital anomalies were found among 125 pregnancies-there has been a  cluster of rare congenital malformations such that imatinib cannot be safely recommended, particularly during the period of organ formation in the baby-first 8 to 12 weeks.

Women interested in getting pregnant while on imatinib and other TKIs should co-ordinate their specific care between oncologists and reproductive endocrinologist so that they attempt pregnancy while in remission for ideally 1-2 years and in the same time minimize the period of time while off treatment. Alternative treatments than TKIs can be used during pregnancy. After delivery, TKIs are restarted and breast-feeding is discouraged as the medicine is excreted in milk. Read more at http://nycivf.org

Melanoma-What Every Woman Need to Know about Fertility and Pregnancy

Women diagnosed with melanoma may require counseling for fertility preservation, fertility treatment and safety of pregnancy after treatment. Melanoma is one of the most common cancers in young adults in the United States. In the US and worldwide, there is  dramatic increase in the incidence  of skin melanomas. Approximately 30,000 women are expected to be diagnosed with melanoma in 2010, one third will be in their reproductive years. Its the most common cancer in young adults 25 to 29 year old. Its more common in white women compared to African Americans and Hispanics.  Approximately  10% of melanomas run in families or are genetically inherited. Treatment of melanoma requires surgery. In advanced melanoma, chemotherapy is added. Dacarbazine-DTIC is an alkylating agent used for treating melanomas. Immune therapy is also used for advanced melanomas- interferon α or IL-2.

In early stages, surgery is the only required treatment. In advanced stages if chemotherapy is used, ovarian reserve may be diminished and this may reduce woman’s ability to get pregnant. The use of immune therapy is not known to affect future fertility. The effects of newer targeted therapies and vaccines on fertility are also unknown.

Melanoma and fertility treatment. The estrogen receptors were found on melanoma cells. Some researchers detected no significant increase in the risk of melanoma after treatment with fertility drugs, except possibly slight increase in risk in women who delivered children before. The relationship between estrogen exposure and melanoma is controversial. Women seeking fertility preservation before exposure to chemotherapy or melanoma survivors desiring pregnancy after completing treatment should consult with a fertility preservation specialist about the risks and benefits of fertility treatment and the safety of pregnancy. The ovarian stimulation regimen can also be modified to minimize estrogen exposure. It may also be possible for women with inherited predisposition to melanoma to avoid transmission to future children through testing of embryos-PGD.

Melanoma and pregnancy. Ten studies including 5600 women found that pregnancy does not reduce survival in women diagnosed with melanoma. Women treated for melanoma who subsequently became pregnant were not adversely affected compared to women who did not get pregnant after treatment. For thin tumors-<1.5mm most experts do not recommend deferring pregnancy. For thicker tumors, physicians may recommend deferring pregnancy for two years as most recurrences take place during that interval. Read more at http://nycivf.org

You are a breast cancer survivor, what next? Roadmap to pregnancy after treatment

Young women treated for breast cancer at risk for decreased fertility  due to exposure to chemotherapy and delaying pregnancy for several years after treatment. Twenty percent of women diagnosed with breast cancer are in their reproductive years. By the year 2010, 2.9 million breast cancer survivors are predicted in the US, approximately 2% of the female population. California, Florida and New York will rank first among states in the number of survivors.

Women considering pregnancy after completing breast cancer treatment  require extensive counseling of risks and benefits as well as discussion  of available options to achieve pregnancy, tailored to their medical and social circumstances. Psychological counseling is also helpful  in coping with stresses of treatment.  I usually start with consultation session to get to know the individual woman as well as information about her breast cancer. During this session I initiate testing for ovarian reserve through blood work and ultrasound. I also present her with printed material to read about ovarian stimulation and pregnancy after breast cancer. With her permission, I also contact her oncologist to discuss assess his or her opinion in relation to pregnancy after breast cancer treatment. I request that the woman or couple visit me few days later to discuss  test results and options for fertility treatment.

Testing & Counseling. 1. Ovarian reserve. This indicates the number and quality of the eggs remaining in the ovary. Its related to the woman’s age, type and dose of chemotherapy received. There is marked variation among women in their ovarian reserve due to genetic factors and type and intensity of chemotherapy. Estimating ovarian reserve may predict response to treatment and chance for success of fertility treatment. Ovarian reserve can be estimated using ultrasound to visualize the tiny follicles in the ovary. Blood tests for markers such as FSH, LH, Estradiol and AMH can  also help in determining ovarian function. Patency of the fallopian tubes is also tested using a hysterosalpingogram. Partner semen analysis is also ordered. 2. Safety of ovarian stimulation. To enhance fertility, stimulation of egg production in the ovary is commonly employed.  Common ovarian stimulation methods result in increase of estradiol. To avoid this increase in estrogen sensitive cancer, we have  shared in developing a protocol that employ a drug that prevent the ovary from making estrogen. When tested this method did not appear to increase breast cancer recurrence. We however do not know the effects of ovarian stimulation on the long term, 5 years or more. 3. Safety of  pregnancy. Studies published so far indicate that pregnancy does not increase the risk of recurrence in women treated for breast cancer. Moreover, some studies even detected reduced risk of recurrence and death due to breast cancer in women who became pregnant. 4. Transmission of BRCA mutation to the baby. Five to ten percent of young women diagnosed with breast cancer carry mutations in BRCA1 or 2 genes. These mutations can be transmitted to their children. It is possible to avoid this transmission by testing their embryos before placing them into the uterus. Pre-implantation genetic diagnosis – PGD was successfully performed in women carrying these mutations.

Options. If pregnancy is judged to be safe, several options for reproduction exist 1. Timed intercourse. Women with regular menstrual cycles and good ovarian reserve, can attempt pregnancy spontaneously for 6 months to a year. Ovulation can be monitored using home predictor kits that test urine for LH hormone. When a surge is indicated by the test, intercourse for the next three days is usually advised.  2. Ovarian stimulation-IUI. Stimulation of the ovary aiming at recruiting two or three eggs can be accomplished using letrozole or letrozole and gonadotropins. This is usually followed by intrauterine insemination when the eggs are judged to be need maturity. This is usually attempted for three cycles. 3. Embryos or oocytes frozen prior to breast cancer treatment frozen / thaw embryo transfer. Women who preserved their fertility prior to cancer treatment can thaw those and transfer one or two embryos into the ovary. This commonly carry a reasonable pregnancy rate for embryos, about 30% per cycle. In case of frozen eggs, they need to be fertilized using ICSI-direct injection of a single partner or donor sperm into the egg. Thawed eggs usually carry lower pregnancy rates than embryos. 4. IVF. In vitro fertilization carry the  highest pregnancy rates of all fertility treatment. Its success, however, depends on age and ovarian reserve. a. Natural cycle IVF. Women interested in avoiding excessive estrogen exposure and cost can consider natural cycle or minimal stimulation IVF b. Ovarian stimulation IVF. In this option the ovary is stimulated to produce multiple follicles, eggs are aspirated , fertilized and  the resulting embryos are transferred into the uterus. 5. Third party reproduction-egg donation and gestational carriers. Donor oocytes are considered in women with very low ovarian reserve or who develop ovarian failure after treatment. The use a gestational carrier is considered for women who cannot carry a pregnancy due to breast cancer or other condition. Woman’s biological embryos are transferred to the uterus of another woman.

Women treated for breast cancer show variability in terms of ovarian reserve after chemotherapy. They require testing for ovarian function and counseling about the most feasible and safe method to get pregnant after treatment.  Read more at http://nycivf.org

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

How to Preserve Fertility after prostate cancer

Prostate cancer is the most common cancer in men-one in 6 men in the US. Treatment of prostate cancer can markedly reduce fertility potential. Its is expected that 217,000 men will be diagnosed with prostate cancer in the US in 2010. Screening for prostate cancer using a blood tests-prostate specific antigen (PSA) resulted in increased diagnosis in younger men. Many men diagnosed with prostate cancer are interested in future fertility. Prostate cancer is diagnosed in 1 in 10,000 men before the age of 39 and 1 in 40 between the ages of 40 and 59. Except in cases of distant spread, survival after prostate cancer approaches 100%. Prostate cancer is more common in men carrying BRCA2 mutations and occurs in younger age.

Cancer in men may affect sperm count and quality, although this is controversial. In general 10% of men diagnosed with cancer are expected to have no ejaculated sperm-azospermia. Up to 50% may have abnormal sperm quality.

Effects of prostate cancer treatment on future fertility in men. Treatment options for prostate cancer include 1. Radical prostatectomy. This procedure can be performed through a large incision or via minimally access surgery-laparoscopy. Surgery can be modified to preserve the nerve fibers responsible for erection thus reducing erectile dysfunction after surgery. Surgery causes block of the vas deferens on both sides leading to obstruction and azospermia. 2. Radiation. External beam radiation affect sperm production from the testes as scattered radiation can damage the sperm producing cells. Placing a radioactive seed inside the prostate-brachytherapy, has minimal effect on sperm production. 3. Observation on;y is possible for selected men diagnosed with prostate cancer.

Options for fertility preservation in prostate cancer. 1. Sperm Cyopreservation. Less than 50% of men diagnosed with cancer preserve their sperm before treatment due to lack of information or counseling. This is a very available and low cost option. One or more samples can be frozen depending on time and initial sperm  counts and quality. Sperm can be frozen indefinitely. If multiple samples were frozen, they can be used for intrauterine insemination. If limited amount of sperm is available or low quality -movement or sperm shape, IVF with injection of sperm into the egg-ICSI is required. Sperm freezing has a good psychological impact on men  during cancer treatment. 2.  Electroejaculation. For men who have erectile dysfunction or inability to ejaculate after surgery, electrical stimulation can induce ejaculation. Sperm quality in this case is likely abnormal favoring the use of sperm for IVF-ICSI. 3. Testicular Sperm Extraction-TESE. Form men with no ejaculated sperm-azospermia, sperm can be surgically obtained from the testes. This is also an option for men who cannot produce sperm and no sperm could be aspirated without surgery. This procedure can be performed during the surgical treatment for cancer. Sperm are obtained in 50-60% of men with azospermia. Sperm obtained are used for IVF with ICSI. Sperm can also be obtained from the duct that convey sperm outside the testes-Microsurgical epididymal sperm aspiration-MESA. The success rate of achieving pregnancy using frozen ejaculated sperm or surgically obtained viable sperm is not different from fresh sperm.

Checklist for fertility preservation in prostate cancer

  • Discuss with your oncologist different cancer treatment options-radical prostatectomy, external beam radiation and brachytherapy or even observation only.
  • If radical prostatectomy is planned inquire about the technique of surgery-open or laparoscopy, nerve sparing procedures and incidence of erectile dysfunction in the surgeon’s hands
  • Ask for more information about the effects of prostate cancer treatment and fertility preservation options from the oncologist or reproductive endocrinologist.
  • If interested in fertility preservation a reproductive endocrinologist or urologist can refer you for semen analysis and freezing (in the same time), interpret the semen analysis and advice about the number of samples to be frozen.
  • If no sperm found-azospermia, surgical sperm retrieval can be performed at the time of surgery for cancer.