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Ovarian Cysts and Fertility

Ovarian Cysts and Fertility

Ovarian cysts are very common during reproductive age women. The cyst has a wall and is full of fluid. Very few of ovarian cysts are cancer after puberty and before menopause. The two most common types are follicular cysts and corpus luteum cysts. These are the result of follicle growth in the ovary (the sac that contains the egg) that either a. does not release the egg and continue to grow or b. releases the egg then the follicle wall now called the corpus luteum closes and reform a cyst. The vast majority of these cysts require just observation as they resolve on their own.

Endometrioma

laparoscopic surgery for endometrioma may reduce ovarian reserve

The other two common benign cysts are dermoid cysts and endometriomas. Dermoid cyst is a developmental cyst that are commonly found in young women. It is very rare for them to become cancer. Larger cysts can twist and become painful as they twist the blood vessels of the ovary. This needs prompt medical attention. Endometriomas are benign cysts full of old blood. The wall of endometrioms is similar to the lining of the uterus-endometrium. They sometimes cause pelvic pain.

Benign tumors of the ovary can also include serous or mucinous cysts, they contain thin or thick fluid, respectively. They rarely become malignant. Border-line ovarian cysts exhibit more activity of the cells lining the cyst wall but lack the invasion seen in cancer. Malignant cysts do exist but are not common before the age of 40.

Evaluation of ovarian cysts include clinical history, pelvic exam, careful ultrasound, color doppler to study blood flow into the cyst and blood work to assay tumor markers. Vaginal ultrasound, can in expert hands, delineate the characteristic appearance of the cyst and can reach an accurate diagnosis in 90% of dermoid cysts and endoemtrioms. Sometimes a follow up of six to eight weeks is needed as the majority of follicular and corpus luteum cysts will disappear during this period. Larger cysts that do not appear during that period may require surgical evaluation, usually using minimally acess surgery-laparoscopy.

Fertility preservation in women diagnosed with ovarian cysts. The most important initial task is to exclude malignancy in an ovarian cyst.

Benign cysts– can be managed using observation every 6 months or ovarian cystectomy. Ovarian cystectomy entails making a cut in the ovary and removal of the cyst and the cyst wall. Removal of the cyst wall, inadvertently remove some of the adjacent ovarian tissue. Sometimes that impairs the future function of the ovary and reduces ovarian reserve and possibly the chance of future pregnancy. This is especially true if the surgery has to be repeated in the future or needs to be done on both sides. If the type of cyst is known with high degree or certainty as in the case of dermoid cysts and endometriomas, the cysts are small and not causing any complaints, young women can elect to observe them until they complete their family. If ovarian cystectomy is planned, discussion of the effects on ovarian function should be  initiated as well as evaluation of ovarian reserve before and after surgery. Ovarian stimulation and egg or embryo freezing can be accomplished prior to surgery. For some women, ovarian tissue freezing can also be performed at the time of surgery.

Borderline ovarian cysts. Borderline ovarian cysts can be treated with cystectomy-removal of the cyst, oophorectomy-removal of the whole ovary or hysterectomy with removal of both ovaries. There is no evidence that one treatment is better than the other in terms of survival. For women who desire future fertility removal of the cyst only is a viable option. If the ovary need to e removed, ovarian stimulation, egg retrieval and embryo or egg freezing can be performed prior to surgery.

Malignant ovarian cysts. Malignant ovarian tumors limited to one ovary, can be treated by removal of that ovary with preservation of the uterus and the other ovary. Unfortunately, those that spread beyond the ovary may require hysterectomy and removal of both ovaries.

If you have an ovarian cyst and surgery was recommended, consultation with a reproductive endocrinologist and oncologist or gynecologist can clarify possible effects of surgery on future fertility. Women then will have the opportunity to understand fertility preservation options available for them.

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Fertility in Women Carrying BRCA Gene Abnormality

Fertility in Women Carrying BRCA Gene Abnormality

Fertility in women carrying BRCA gene abnormality may be reduced

Women carrying BRCA gene abnormality frequently consult with reproductive endocrinologists for fertility treatment or preservation.  Women referred to test the BRCA gene for mutations based on ancestry, family history and type of cancer diagnosed in her family. If a mutation is found the lifetime risk for breast cancer is 70% and ovary cancer is 40%.

Fertility in women with BRCA mutations maybe reduced in reproductive age women because of the mutation itself, procedures used to reduce the risk of cancer or cancer treatment if they develop cancer.

 

BRCA mutation and Fertility

BRCA mutation and Fertility

Ovarian Reserve and Response to Ovarian Stimulation

Women carrying a BRCA mutation may require ovarian stimulation using fertility medications for

  1. Preservation of fertility through egg freezing or embryo freezing prior to prophylactic removal of both ovaries,
  2. Preservation of fertility after the diagnosis of breast cancer and before chemotherapy or
  3. An incidental fertility problem unrelated to BRCA mutation.

Ovarian reserve and response to fertility medication is one of the most determinants of success of fertility treatment or preservation.

Although it was suggested that women with BRCA mutations respond more modestly to fertility medications, this was not proven. When women carrying these mutations were compared to relatives with no mutations, there were no differences in the number of deliveries and the need for fertility treatment. Also in a study of 260 Ashkenazi Jewish women with ovarian cancer and 331 controls, unselected for age or family history of the disease. Pregnancy success was similar for 96 mutation carrier and 164 non-carrier cases and controls.

Fertility & fertility treatment

Its unlikely that fertility or fertility treatment will increase the risk for breast cancer in women with BRCA mutations. 1380 women diagnosed with breast cancer and carrying BRCA mutations were matched 1380 women without breast cancer and carrying BRCA mutations. 16% reported fertility problems, 4% used fertility medications and 1% used IVF. There was no difference between women who developed breast cancer and those who did not regarding history of infertility and the use of fertility medication. The type of fertility medicine-oral or injection medication also did not change the risk for breast cancer, irrespective if women had children before or not.

Interestingly, there is significant excess of females among the offspring of female carriers of BRCA1 and BRCA2 mutations-higher female to male ratio.

Avoiding BRCA transmission to babies (PGD)

Women interested in getting pregnant should be counseled to the risk of transmission of mutation to future children. Both men and women carrying the mutation are at a significantly increased risk of cancer. It is very possible to prevent this transmission if the eggs or embryos are tested before replacement into the uterus in women undergoing in vitro fertilization – IVF Eggs are tested by polar body biopsy (this is a small cell attached to the egg and carry chromosomes representative to those of the egg). Embryos are tested by testing one cell of a 6 to 8 cell embryo. Testing has many medical and ethical dimensions and is better handled by providers specializing in these areas.

Pregnancy

The risk of breast cancer may increase with multiple pregnancies and deliveries in women carrying BRCA2 mutations. In BRCA1 mutation carriers, late menarche and breast feeding reduces the risk for breast cancer. The effect of pregnancy on cancer risk though was not confirmed in multiple studies.

Read more to learn about different methods for preserving fertility after BRCA diagnosis.

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Egg Reserve and Infertility

Egg Reserve and Infertility

Egg reserve means the number and quality of eggs remaining in the ovaries at a given age. It reflects the fertility potential of a woman irrespective of the cause of infertility, even male factor.

Benefits of Testing for Egg Reserve

Testing for egg reserve results should be interpreted with caution. Abnormal values should not be a cause for denying fertility treatment because the predictive power for pregnancy with own eggs is modest. For women, ovarian reserve tests give women insight into the chance of pregnancy with there own eggs. It also may indicate the need to promptly avoid delay in seeking fertility treatment.  For reproductive endocrinologists, the tests have value in designing fertility treatment and selecting the most appropriate fertility treatment protocol. They predict response to fertility medications and allow infertility specialists to select treatment protocol and gonadotropin dose. Egg reserve also predicts the number of eggs retrieved for IVF or egg freezing.

Egg Reserve: Egg Number

Although the number of eggs in the ovaries decrease with age there is significant individual variation in initial number endowed in the ovaries and the rate of decrease. Some young women has low egg number and older with large number of eggs. Ovarian reserve tests are used to estimate this number.

Egge reserve: the number of eggs in the ovaries drops with age

Egge reserve: the number of eggs in the ovaries drops with age

History

Medical history may indicate low egg reserve in women with prior excision of ovarian cysts, endometriosis of the ovaries,  women who smoke and with family history of early menopause

Antral follicle count

The number of antral follicles in the ovaries (the structures that contain the eggs) can be seen and counted using vaginal ultrasound. Performed by an experienced reproductive endocrinologist, it can accurately estimate ovarian reserve. Low count e.g <10 in both ovaries points to low reserve.

Day 3 FSH, Estradiol

FSH is produced by the master gland in the base of the brain. Estradiol is made by the follicles themselves. Measured in the second or third day of menstrual cycle, high FSH (>12) of high estradiol (>75) points to low egg reserve.

Antimullerian Hormone (AMH)

AMH is produced by the cells surrounding the eggs in small follicles and is a more direct measure of egg reserve than FSH. It can be accurately measured any day in the cycle with  little variations in between cycles. Levels <1.5 ng/dL generally indicates low egg reserve. It correlates well with antral follicle count.

Genetic Screening

Low egg reserve in few women is due to a genetic cause. Fragile X syndrome is a genetic disease that causes low egg reserve and mental deficiency in newborn males. Chromosomal abnormalities e.g Turner syndrome, translocations are also associated with low egg reserve. Genetic screening is performed using a simple blood test before starting fertility treatment.

Egg Reserve: Egg Quality

What does egg quality means ?

Good quality eggs are chromosomaly normal (has 23 chromosomes). The most important factor that prevents the achievement of pregnancy or leads to early miscarriage is an abnormal egg (has extra or missing chromosome or piece of a chromosome). Many eggs at any age in any woman are abnormal and the normal eggs are the ones that are successful in being fertilized with sperm, implant and achieve a pregnancy. These errors takes place when the original cell that produce the eggs divide to reduce the number of chromosomes to half. The division (meiosis) is many times unequal leading to an egg with an extra or missing chromosome.

Age and egg quality

The ovary releases better quality age earlier in life and lower quality age later, for unknown reason. Female age is the most important indicator for egg quality, chance for spontaneous pregnancy and after fertility treatment. Older women need to try longer to achieve pregnancy and at an increased risk for miscarriage, ectopic pregnancy and delivering a baby with chromosomal abnormalities e.g Down Syndrome. This effect of age become clinically evident at age 30 or even earlier. Age is more important than the number of eggs in the ovaries. Young women with few eggs in the ovary are more successful in getting pregnant than older women with many eggs in the ovary.

Meiosis

Meiosis

Testing for egg quality: PGD

Age is the only available noninvasive method to estimate egg quality. Healthy eggs cannot be identified using any non invasive method. It is possible to identify chromosomal errors in the egg during IVF fertility treatment after biopsy of the first polar body of unfertilized egg or after removing one cell from an embryo after the egg is fertilized then test this material for chromosomal abnormality. This process is called PGD or preimplantation genetic diagnosis. It is important to remember that PGD is not proven so far as method of enhancing fertility potential. It simply detects if the egg or embryo is chromosomaly normal or not but will not make an unhealthy egg healthy.

Read more about ovarian reserve and low response to ovarian stimulation in my review here.

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