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by Kelly Baek, M.D.
Deciding to build a family as a single woman or as a lesbian couple requires planning. Women who have not tried to conceive or who have not been exposed to sperm are not by definition infertile, unless there are other, medical obstacles to pregnancy, such as advanced maternal age or blocked tubes. For that reason, a basic fertility evaluation should be considered prior to trying to conceive in order to optimize pregnancy success when using donor sperm. This is a general overview of clinically relevant points when proceeding with an evaluation and treatment.
Natural pregnancy rates the first six months of trying to conceive are approximately 20% per month. This percentage decreases dramatically to less than 5% after 6 months. Pregnancy rates decrease with advancing maternal age for the following reasons. Unlike men who produce sperm throughout their life, women are born with a certain number of eggs. Every month, even though only one lead follicle develops and ovulates, hundreds of eggs are lost. Every woman is allotted a different number of eggs at birth and certain lifestyle factors such as smoking as well as medical or surgical issues can increase the attrition of their eggs. These factors ultimately impact ovarian reserve as well as fertility. Advancing maternal age is associated with increased chromosomally abnormal eggs and therefore subsequent lower pregnancy rates and increased miscarriage rates. It is important for couples to assess their ovarian reserve because it may change the order of whose eggs should be used first when both partners desire genetic offspring. Occasionally, the younger partner can be found to have a lower ovarian reserve and therefore should conceive sooner.
Women who have irregular menstrual cycles may not ovulate and should seek an assessment prior to attempting conception. I have worked with many women who have tried for months only to discover they were anovulatory and could not have conceived because they were not releasing any eggs. To avoid wasting time as well as money and other resources, undergoing a basic evaluation first is prudent especially, if there is any history of menstrual irregularities, family history of early menopause, history of sexually transmitted diseases or chronic medical conditions or history of pelvic surgery.
A basic female fertility evaluation includes ovarian reserve testing, evaluation of anatomy, and hormonal profile. Women with irregular menstrual cycles or medical conditions may require additional testing to determine both diagnostic and treatment algorithms.
Ovarian reserve is best assessed on the second or third day of the menstrual cycle with estradiol and follicle stimulating hormone, FSH, levels and a pelvic ultrasound measuring antral follicles. Estradiol and FSH levels fluctuate monthly and reflect the cohort of eggs for each month. Anti-Mullerian Hormone, AMH, levels can be drawn at anytime in the menstrual cycle unlike estradiol and FSH levels to assess ovarian reserve and is another test of ovarian reserve. Diminished ovarian reserve is associated with elevated FSH levels, lower AMH levels and lower number of antral follicles. Women with diminished ovarian reserve, regardless of age, should create a treatment plan with their reproductive endocrinologist when trying to conceive.
Hysterosalpingogram is a radiologic study where a catheter is placed into the uterine cavity and fluoroscopic dye is used to assess for possible anatomic causes for infertility. It specifically examines the uterine cavity for possible congenital anomalies, polyps, or fibroids, which could hinder implantation or negatively impact pregnancy and the fallopian tubes for possible obstruction or damage. Tubal disease prevents fertilization because sperm and eggs may not meet and increases the risk for ectopic pregnancies. Presence of significant hydrosalpinges (dilated fallopian tubes) which may be patent, are associated with a 50% lower pregnancy rate.
If tubal disease and/or other factors are uncovered in the evaluation, in vitro fertilization, IVF, should be considered to bypass the fallopian tubes and to increase fertilization. Sometimes intracytoplasmic sperm injection, or ICSI, will be recommended. With ICSI, a selected spermatozoa is injected into the egg to insure fertilization.
Thyroid stimulating hormone, TSH, and prolactin levels should be assessed, especially in women who have menstrual irregularities. Thyroid profiles can change overtime. Hypothyroidism, where TSH levels are elevated, is associated with lower pregnancy rates and increased miscarriage rates. The medical endocrine society recommends that women who are trying to conceive or who are pregnant should maintain their TSH levels below 2.5 mIU/L. Normal TSH levels for women who are not trying to conceive are 4-5 mIU/L. Prolactin levels fluctuate throughout the day and are affected by many factors including eating and sexual activity. Therefore, if prolactin levels are elevated, a fasting morning prolactin level with no sexual activity the day before should be drawn to confirm a truly elevated prolactin level.
Finally, women who are trying to conceive should undergo a preconception panel that includes infectious disease screening, testing for immunity to chickenpox and rubella, and ethnicity based genetic screening. Women who are non-immune to rubella or chickenpox should undergo vaccinations prior to conceiving. Women who are found to be carriers of genetic disorders such as cystic fibrosis should be evaluated by a genetic counselor to review their individual risks for having a child affected with cystic fibrosis. The sperm provider needs to be tested whenever a woman is discovered to carry a genetic disorder to minimize the risk of conceiving an affected offspring.
It is ideal to maintain a normal body mass index (BMI), to eat a well balanced diet, to sleep regularly and to exercise regularly. Weight fluctuations and irregular sleep patterns can cause ovulatory dysfunction in a natural cycle. This is evident during periods of stress, for example, when travelling across time zones or studying for exams. In a natural cycle, women can find that their menstrual cycles are delayed or unpredictable during those times.
Folic acid supplementation of a minimum of 400mcg should be taken daily prior to conception to reduce the risk of neural tube defects in the fetus. A multivitamin or a prenatal vitamin should also be taken when trying to conceive.
I advise my patients to minimize their intake of sugar, caffeine, and alcohol. If patients are working with an acupuncturist, I consult with the acupuncturist to ensure that they specialize in fertility and avoid certain points during the luteal phase. I have found by coordinating my treatment plans with acupuncturists directly, patients benefit from the team effort and experience less stress because they do not need to function as a messenger between their western and eastern doctors.
Choosing a Sperm Provider
One of the biggest decisions is choosing a known or an anonymous sperm provider. Every state has different laws and a reproductive attorney should be consulted when using a known donor to avoid any issues with custody or visitation in the future.
When using a known sperm provider, there are several medical and legal decisions to consider. Still the best first step is to have the sperm provider undergo a semen analysis. Healthy appearing men can be azospermic, have no sperm in their ejaculate, or can have severely compromised semen parameters. This first step saves time and resources.
Known donors can then undergo FDA infectious disease testing at the time they produce their specimen to be frozen and quarantined for use. Once their post-quarantine FDA infectious disease screening results are available, the frozen sperm are released for use with reproductive techniques such as intrauterine insemination (IUI) or in vitro fertilization (IVF). The benefits of working with a fertility center when using is known sperm donor is to protect your legal rights as well as protect your health from potential infections.
When using an anonymous sperm donor from a sperm bank, it is important to consider the following questions:
- Is the donor retired or active. Active donors are more available for additional testing if you are a carrier of a genetic disorder.
- The number of children you desire should be taken into consideration especially when choosing a retired donor.
- How many potential offspring can be attributed to this donor throughout how many families.
- If you purchase an excess number of vials and store them at the sperm bank, some banks will buy them back when you are done building your family as long as the vials never left their facility.
- Another question to ask is whether the sperm donor allows contact in the future. Contact would most likely be through the sperm bank for reasons such as changes in their medical history and other helpful information for your child(ren).
Every state has different laws and a reproductive attorney should be consulted especially if you are unmarried or if you are using a known sperm provider. Without a contract in place, it can be difficult for women who are not the genetic parent to claim custody rights when relationships dissolve. Even when reciprocal IVF is used, where one partner is the egg provider and the other partner is the gestational carrier, the gestational carrier’s custody rights may be difficult to support if they were designated gestational carriers and not partners on their IVF consent forms. Therefore, due to the subtle nuances and the state-to-state differences, it is prudent to work with a reproductive attorney.
Natural Cycle/ IUI
Women who have regular menstrual cycles whose fertility evaluation is normal may start with natural IUI cycles. IUI’s are performed the day following detection of ovulation using an over the counter ovulation predictor kit. The benefit of an IUI is that the washed sperm are placed directly in the uterine cavity. This bypasses sperm lost in the vaginal vault and the cervix. Estradiol and progesterone levels can be assessed several days following the first IUI to determine if hormonal supplementation is needed and to document ovulation. Urine pregnancy tests can detect a positive result fourteen days following the IUI.
Clomiphene Citrate/ IUI
Clomiphene citrate is an oral tablet that is usually prescribed in the early follicular phase for five days in dosages ranging from 50 mg to 200mg. Clomiphene citrate is an appropriate first choice in women who have a type of infertility called polycystic ovarian syndrome and who do not ovulate regularly. Clomiphene citrate works indirectly by preventing the hypothalamus from detecting the increased estrogen levels from the developing follicle. This results in an increase in the secretion of gonadotropin releasing hormone, GnRH, which stimulates the pituitary to secrete more follicle stimulating hormone, FSH, to stimulate the ovaries.
Clomiphene citrate should not be used in women with hypothalamic amenorrhea because this medication requires an intact hypothalamic-pituitary-ovarian axis. In a small percentage of women, visual disturbances or severe headaches can occur. In these instances, you should contact your physician and stop the medication. Finally, clomid can negatively impact upon your endometrial lining and cervical mucus, causing a thin lining that could hinder implantation and or thick cervical mucus that would require an intrauterine insemination to bypass the cervical factor. Therefore, clomid is prescribed oftentimes with estrogen supplementation.
Women may monitor for ovulation using an over the counter ovulation predictor kit to time the intrauterine insemination. Alternatively for women who have difficulty detecting a LH surge or who have ovulatory dysfunction such as polycystic ovarian syndrome, or who are at risk for high-order multiples or a complication from fertility medications known as ovarian hyperstimulation syndrome (OHSS) may be monitored by their physician with ultrasounds. The ultrasound measurements of follicles 18-20mm would be used to time ovulation trigger with HCG injection or to cancel a cycle should too many follicles develop to avoid the risk of multiple gestations or OHSS. An intrauterine insemination is then performed 24-36 hours following HCG injection. If an ultrasound is performed at the time of the IUI, the decision can be made whether or not a second IUI would be helpful. If all the follicles have collapsed, a second IUI would not improve fertilization. In cases where some of the follicles remain, a second IUI is recommended because washed sperm survive for approximately 24 hours and may no longer be viable when the additional follicle(s) ovulate.
Injectable Gonadotropins/ IUI
Exogenous FSH hormones stimulate the ovaries directly thereby promoting the growth of multiple follicles. Unlike in IVF where the number of embryos can be limited, superovulation with injectable FSH needs to be monitored closely to minimize the risk of high-order multiple gestations such as triplets and the risk of ovarian hyperstimulation syndrome by suppressing the development of too many follicles. In cases where a high risk for OHSS or high-order multiples exist, the cycle can be cancelled and the IUI not performed. When follicles are 17-18 mm in size, ovulation is triggered with a HCG injection and the IUI scheduled.
In Vitro Fertilization
When tubal disease exists, IVF is the best option. At the beginning of every menstrual cycle, several antral follicles develop and from these, in a natural cycle, one follicle emerges as a dominant follicle and only one follicle ovulates. The remaining follicles regress. Therefore, many eggs are lost monthly even though only one egg ovulates.
In IVF, the goal of superovulation with gonadotropins is to stimulate the growth of the antral follicles in a synchronous manner so that they grow and mature together. In a natural cycle, the pituitary releases enough FSH to stimulate the growth of one follicle. In an IVF cycle, exogenous FSH and LH hormones are injected to promote the growth of multiple follicles. Women are monitored with blood work and ultrasounds to titrate their medication dosages and to determine when to trigger ovulation for the egg retrieval.
Women are given IV sedation by anesthesiologists and their follicular fluid is aspirated under ultrasound guidance. The fluid is examined by embryologists who identify the eggs in the follicular fluid. Following the aspiration, women start progesterone supplementation and oftentimes are given a course of antibiotics and or steroids. Progesterone supplementation continues until 7-9 weeks gestation.
The decision to use intracytoplasmic sperm injection, ICSI, where an individual selected sperm is injected into the egg to increase fertilization rates is based on a number of factors such as egg characteristics.
Normal fertilization is assessed on the morning following the egg retrieval and determined by the presence of two pronuclei; one nucleus from the egg and the other from the sperm. The embryos are cultured for three to five days before embryo(s) are transferred into the uterine cavity. Excess high quality day five embryos, blastocysts, can be frozen for future use.
Reciprocal In Vitro Fertilization
Reciprocal IVF is an opportunity for both partners to share in the experience. Partners’ menstrual cycles are synchronized using birth control pills and/or lupron. The partner who will be carrying the pregnancy is known as the gestational carrier. The gestational carrier takes estrogen to build her endometrial lining. The partner who will provide the eggs is known as the egg donor. The egg donor undergoes the IVF process of superovulation of her eggs with injectable medications. When the egg donor’s ovulation is triggered with either HCG or Lupron, progesterone supplementation is started for the gestational carrier. Progesterone convinces the body of the gestational carrier that she ovulated and her endometrial lining undergoes the necessary changes to prepare for implantation. Once the eggs are harvested, they are fertilized with donor sperm and transferred into the gestational carrier after three to five days. Excess high quality blastocysts can be cryopreserved for future use.
Conceiving with eggs from an egg donor outside of the couple is associated with pregnancy rates of upwards of 65-70% because egg donors are young and have ovarian reserve tests that show a high number of antral follicles and age appropriate day 2 estradiol and FSH levels. Once egg donors demonstrate having a good ovarian reserve, they are screened by a psychologist and by a geneticist. Then, they have a consultation with a reproductive endocrinologist who takes a medical history and performs a physical exam. At that visit, they are screened for infectious diseases and genetic disorders. They also undergo urine drug screens.
Once legal contracts between the egg donor and the intended parents have been completed, the egg donor’s menstrual cycle is synchronized with the recipient. This synchronization process is identical to the one described above in reciprocal IVF.
Pregnancy rates using frozen eggs depend upon the age of the woman when her eggs were retrieved. Eggs frozen at a younger age are associated with higher pregnancy rates. The salient points to consider when exploring egg freezing is to research the experience of not only the reproductive endocrinologist but also the scientist who will be freezing the eggs. Find out which method of freezing their center uses, either 1) slow or 2) vitrification. Most centers are now primarily vitrifying the eggs into a glass-like stage thereby avoiding ice crystals and risks of fracturing eggs which are challenges faced by the slow freeze method.
Building a family is an exciting endeavor. Working with a fellowship trained board certified reproductive endocrinologist at the beginning of the journey allows for careful evaluation prior to starting treatments and oftentimes expedites the time to success.
Kelly Baek, M.D. is a board certified physician in obstetrics and gynecology at California Fertility Partners