Men making sperm and women losing eggs, Is it nature's fair task

Men make a difficult to comprehend one to two hundred million sperm per day.  Women, on the other hand, are forever losing eggs.  In fact, women have their maximum number of eggs before they are even born.  A baby in her mother’s uterus has 7 million eggs.  By the time she is born, only 2 million of these eggs will have survived.  By the time a women has her first menstrual cycle, only 300,000 of these eggs remain. These eggs are steadily lost in a woman’s twenties and early thirties.  By the time a women is in her mid to late thirties, the loss of eggs begins to accelerate and each year more eggs are lost than the year before.  So what’s a woman to do?

We can’t turn back the clock, nor can we?  New technologies have been developed to allow women to freeze their eggs when they young, and use these eggs when they are ready to have children.  Eggs that are frozen do not age, and can be used may years in the future.  For women currently in their 20’s and early 30’s, this option is no longer just a pipe dream; it is a reality.  In fact, more and more women are being proactive and choosing this option in order to preserve their fertility and be able to make reproductive choices on their own timeline, and not in accordance with their biological clock.

The process takes a few short weeks, and the eggs can remain frozen until they are ready to be used.  This allows women to pursue their life goals within the timeframe that they desire, not being bound by the rules that until the last few years have limited the window of fertility. Women no longer need to worry that every day they are losing 20 eggs while the men they know are making hundreds of millions of sperm.

There are many questions in the mind of egg donor, let’s we answer some basic question about egg donation.

Who are the recipients?

Couples generally choose to use donor eggs because they're unable to conceive a child with the female partner's own eggs. There are many reasons that a woman may not be able to conceive with her own eggs, including older age, early menopause, poor-quality eggs or previous cancer treatments that damaged the ovaries. Frequently, recipients have already been through extensive fertility treatments without success.

What's involved in the screening process?

You will be asked to complete a detailed questionnaire about your background and your medical, family and personal history. After that is complete and has been reviewed by our staff, we will call to arrange screening appointments with our psychologist and genetic counselor. The last step in the screening process is a physical examination with a doctor and laboratory tests.

How much time is involved?

The screening process generally takes a few weeks to complete. You will speak to the Egg Donor Program coordinator by phone and come into the office for a few short visits at our Mount Zion location. Once you're chosen as an egg donor, a cycle takes approximately four weeks.

During a two-week period, you'll come to the clinic about seven to 10 times for ultrasound monitoring and blood tests. These appointments generally require a 15- to 30-minute visit in the morning. The day that you are scheduled for the egg retrieval, you'll be at our clinic for a large portion of the day. Most donors are able to continue to work or go to school during the process.

Will I need to give myself shots?

Yes. The shots are done at home. You can do them yourself, or have a friend or family member help you. We will teach you how to mix and administer your medication in our office.

Are there possible side effects and risks?

As with any medical procedure, there are possible side effects and risks. Many women feel very minor or no discomfort during the donation cycle. Others have varying symptoms that typically resolve after the egg retrieval procedure. Some donors may feel bloating, pressure, abdominal pain and swelling, breast tenderness and moodiness from the hormone medications, which will go away by the next menstrual period. Severe side effects are rare and will be discussed with you in detail by a doctor before you join the program.

1.       Injection side effects and risks:  The blood tests and hormone injections are usually well tolerated. However, some women experience pain, redness or minor bruising at the injection site. Allergic reactions are rare.

2.       Medication side effects and risks:  There is a small risk of ovarian hyper-stimulation syndrome (OHSS) developing during an egg donation cycle. OHSS generally occurs after the egg retrieval and involves enlargement of the ovaries, significant increases in fluid retention within the abdomen and concentration of the blood within the blood vessels.

In its more mild form, OHSS can be uncomfortable but resolves within several days. The severe form, which occurs in about 1 percent of donor cycles, may require hospitalization for monitoring. While the condition is serious, it usually lasts no more than one week.

3.       Procedure side effects and risks: The egg retrieval procedure is guided by transvaginal ultrasound. The risk of serious complications from this procedure is rare - about 1 in 1,000. Serious complications involve bleeding that requires observation in the hospital, blood transfusion, or both, as well as damage to internal organs and infection.

4.       Other side effects and risks: To date, evidence doesn't suggest any increased risk of breast or ovarian cancer from serving as an egg donor. There is no evidence of increased risk of infertility.

Are there any restrictions during the process?

You can get pregnant during the egg donation process, so we ask that you abstain from intercourse during the process.

Your ovaries will become enlarged during the egg donation process. We ask you to refrain from high-impact activities such as running, mountain biking and jumping until several weeks after the egg retrieval. After approximately one month, your ovaries will return to their normal size.

Can I become pregnant during treatment?

Yes! It's very important to avoid intercourse from the time you start the hormone medication until three weeks after your egg retrieval. This will prevent an unwanted pregnancy and ensure the cycle goes as planned.

Will it impact my fertility or deplete my eggs?

No. The procedure itself doesn't have any impact on your future ability to have children. Women are born with about 2 million eggs. Each month, a group of eggs begin the maturation process, but the body selects only one egg each cycle to ovulate, while the rest are absorbed by the body. Fertility medications "rescue" some of these excess eggs that the body would have ordinarily discarded.

Can I still work or go to school?

Although the egg donation process requires you to adhere strictly to your medication and appointment schedule, most women are able to continue with work and school without difficulty.

However, you must take the medication as instructed, and on time. You must be on time for all monitoring appointments, and you must arrange for transportation to and from the egg retrieval. This means you will need to make your egg donor cycle a top priority during the few weeks that it occurs, and you may have to reschedule other events, classes or work times as necessary.

How many eggs does the average donor produce?

Egg production depends on the individual and how they respond to the medication; the number of eggs produced by a donor can be as low as five and as high as 35 or more.

How long will it take for my body to return to normal after egg retrieval?

You should anticipate a menstrual period within 10 days after you donate. Following the next menstrual cycle, your body should be back to normal. 

How often can I donate?

We allow up to four donations, each at least three months apart.

What are my responsibilities if I agree to become a donor?

The responsibilities of ovum donors are:

·         Be truthful in all portions of the donor screening process.

·         Follow the doctors' orders during the treatment cycle.

·         Adhere strictly to your medication and appointment schedule. You must take the medication as instructed and on time, and arrive for all monitoring appointments on time. This means you must make your egg donor cycle a top priority during the few weeks that it occurs.

·         Arrange for transportation to and from the egg retrieval procedure.

·         Abstain from sex from the time you start the hormone medication until three weeks after your egg retrieval, to prevent an unwanted pregnancy and make sure the cycle proceeds as planned.

Do I have legal responsibilities to any child born?

When you agree to donate your eggs, you are giving up all rights and responsibilities associated with the eggs and any child born as a result of them.

Will the recipients know me or meet me?

Most egg donor arrangements are anonymous, meaning you won't know the recipients and they won't know you. Information about you is shared with the recipients in a non-identifying manner. For example, we share the following information: your blood type, ethnic background of your mother and father, height, weight, body build, eye color, hair color and texture, years of education, occupation, special interests and family medical history. Pictures you give us will also be shared with potential recipients. We will not share your last name, address, telephone number or email address.

We are committed to creating egg donation arrangements that fit the personal needs of both donor and recipients. Some donors and recipients are interested in meeting each other and we support that process, if all parties are willing. On your application, you will indicate whether you're willing to meet the recipients, and whether you would be willing to meet their child when the child is an adult.

Can I donate more than once?

Yes. If all goes well with your first egg donation cycle, we would be happy to have you come back and donate again. Repeat donation may take less of your time, because you will have already completed the initial screening process.

Investigation and Clinical Approach of Recurrent Implantation Failure

Recurrent implantation failure (RIF) derives from the practice of IVF. The ability to identify implantation failure after the transfer of embryos raised the possibility that there exists a patho-physiological state leading to repeated implantation failure. RIF can be defined as the repeated lack of implantation after the transfer of embryos. Prior to IVF, treatment resulted either in a pregnancy or not. IVF added the ability to further compartmentalize the treatment process so that it became possible to know when an embryo was transferred and if an implantation occurred. Hence RIF became a possible clinically identifiable phenomenon. The relevance of defining such a problem lies in the ability to diagnose patho-physiological conditions, which might be amenable to treatment and thus increase the implantation rate thereby increasing a couple’s chance of conception.

Many practical procedural problems exist when trying to define implantation failure. One limitation when defining implantation and implantation failure is that at present, implantation can only be determined by a rising quantitative hCG level which occurs a number of days after implantation has actually occurred or failed. There remains a time-frame which cannot be further compartmentalized and thus limits the ability to precisely define the cause of implantation failure. Thus, for practical purposes, implantation is defined as a rise in the quantitative hGC level determined at some point after embryo transfer. The most accurate way to determine this would be to do daily serum HCG levels starting after embryo transfer. But again practicality dictates that the first level is drawn at some point after embryo transfer and for many programs this is usually 10–14 days after hCG is given.

The timing of when the first hCG determination is performed will affect the implantation rate. The earlier the first hCG determination is done, the lower the failed implantation rate will be since some pregnancy losses will occur prior to the hCG determination for those programs measuring it later in the cycle. Any definition of RIF requires a standardization of the time from embryo transfer to the time used to determine a positive hCG level. The definition also needs to establish what will be considered a pregnancy when using hCG. For example, will any value above the threshold value be considered evidence of implantation or will there need to be rising hCG levels? Finally, the day of embryo transfer needs to be established. For example, suppose there was a preventable cause of failed implantation that occurred at the morula stage. Programs transferring day three embryos would have a higher failed implantation rate than those programs transferring blastocyst embryos.

The accuracy of a clinical definition is to a large extent determined by the simplicity or, conversely the complexity, of the problem. A physiologic process that has a single factor is easy to define in its entirety. A pathological process that alters the physiology of the process in question may be caused by a single factor and, if measurable, the definition of the disease process is simple and accurate. The thesis of this manuscript has two prongs. First, implantation is extremely complex and highly redundant. Continuation of the species is evolutionarily a high priority. Therefore, the evolutionary process has preserved the ability to implant through accruing a number of individual processes, many of which are, in and of themselves, not necessary, but collectively contribute to a maximum chance for implantation. Second, because of the complexity and redundancy of implantation, assigning etiologies for implantation failure and RIF will be difficult.

There are some processes involved in implantation which are simple and absolutely required for implantation to occur. But there are many processes which are not necessary but contribute to implantation. Therefore, the problem with implantation failure as well as RIF is not in defining the problem, which is self-evident, but in assigning causality to the phenomenon. Some causes of IF and RIF will be a single factor. Their identification and their contribution will be easier to discern. However, implantation failure and RIF may be a result of a threshold phenomenon whereby there are a multitude of factors required for maximum implantation efficiency. A failure of any one of these factors might, or might not, reduce the overall implantation rate. But to reach a state whereby implantation failures, or implantation fails repeatedly, might require errors in a number of factors and might not be the same factors for each case of IF or RIF. The identification of this problem becomes complex and very difficult to approach experimentally.

Any deviation from or interruption of the normal structure or function of any part, organ, or system, or combination thereof, of the body that is manifested by a characteristic set of symptoms or signs, and whose etiology, pathology, and prognosis maybe known or unknown. Implantation failure and especially to recurrent implantation failure demonstrates just how difficult it becomes to define a disease. There are two ways of approaching a definition for a normal implantation rate: evaluate spontaneous pregnancy rates in fertile couples, or evaluate implantation rates when using donor oocytes. There are many factors intervening when couples have intercourse which could result in a less than perfect system so that more than 50% of the cycles do not result in a pregnancy. Therefore, using the natural pregnancy rate in maximally fertile women does not provide the best definition of a normal implantation rate.

IVF provides a more definable system since it involves oocyte, sperm and, endometrium. For this more defined system, the relevant statistic is not normal implantation rate but rather, the maximum implantation rate. Any deviation from this maximum implantation rate would represent a compromise that is, by definition, a disease. Identifying the maximum implantation rate requires evaluating implantation rates obtained through the use of normal oocytes, sperm, and endometrium when the IVF procedure is done by the technically most adept IVF units. This condition is frequently met for women using donor oocytes for age-related ovarian failure. The implantation rate for the double embryo transfer patients was equally high at 56%. It would appear that the maximum implantation rate for IVF is between 40% and 60%. For IVF programs with substantially lower implantation rates, the problem may be technical related to either the clinical or laboratory components of the program. Until a program’s implantation rates meet industry standards, evaluating the patient for problems with implantation failure will be premature.

Defining the term “recurrent” is very challenging, analogous to defining infertility or recurrent pregnancy loss. A problem when using pregnancy rates based upon number of transfer cycles relates to the variability of the number of embryos transferred on any given cycle, the quality of the embryos transferred, and the day of embryo transfer. Defining recurrent implantation failure as three unsuccessful IVF attempts actually defines RIF in terms of failed IVF cycles and does not address the issue of implantation rates. Some patients may have a large number of poor quality embryos transferred for a given IVF cycle; whereas, others may have only one or two embryos transferred. Thus, defining RIF in terms of pregnancy rate does not allow an evaluation of the implantation rates. Also, the day of transfer greatly impacts the pregnancy rate since blastocyst embryos have a higher implantation rate than day three embryos.

Therefore, time to pregnancy should be shorter for cycles with blastocyst transfers and especially if many blastocysts are transferred on a given cycle. For example, transferring three blastocyst embryos should result in a pregnancy sooner than transferring only a single blastocyst embryo. The definition of RIF would be fewer transfer cycles for multiple optimal embryos transferred per cycle than for either poorer quality embryos, high quality embryos transferred on day three, or fewer blastocyst embryos per cycle. Age also has an impact on the pregnancy rate and is a known factor for implantation failure. Thus, defining recurrent differs depending upon the age of the population studied. Finally, the choice of the number “three” deserves some attention. For three to be the operational number of IVF cycles, there needs to be some correlation with that number and the incidence of implantation failure. For example, the cycle fecundity needs to decline after three cycles of IVF if RIF is defined by the number of cycles for transfer. Where there is no implantation failure, the cycle fecundity rate remains constant. The cycle fecundity rates of 36.2% for each of the first four cycles of donor oocyte embryo transfers.

However, cumulative pregnancy rates for IVF have demonstrated a decline in cycle fecundity with successive failed IVF cycles. A clinical pregnancy rate of 19.0% for the first IVF cycle, 17.4 for the second, 11.8 for the third, 10.8 for the fourth, and less than 6% for the next three successive cycles of IVF. Defining RIF after three cycles of IVF with this data is problematic given the fact that is seems the number should be either two or four cycles of IVF. Furthermore, notes an even more dramatic decline in pregnancy rates with successive IVF cycles where the embryos transferred were blastocyst embryos. The cycle fecundity rates were 36% for the first transfer, 19% for the second, and 9% for the third. Given this data, RIF may need to be defined as failed two or even one cycle of transfers with blastocyst embryos.

A second method of defining RIF uses the number of embryos transferred. All consecutive pregnancies from a large IVF program were analyzed to determine the total number of embryos that had been transferred to achieve each pregnancy. The number to achieve 80% of the pregnancies was 8 and for 95% of the pregnancies it was 12. Arbitrarily defining normal at the 95 percentile, RIF was defined as having failed to achieve a viable pregnancy if more than 12 embryos had been transferred. The patients participating in this study were all infertility patients and, thus, the pregnancy rates were not maximal as they might have been had donor oocyte recipient patients been used. The pregnancy rates and implantation rates were below what they are today, and these pregnancies were achieved using day three transfers, not blastocyst transfers. Therefore, the number used to define RIF would be lower today and depend upon whether day three or blastocyst transfers were being considered.

Any definition of RIF will be found wanting given the complexity and redundancy of the implantation process. However, a working definition of RIF can be based upon the number of embryos transferred. The definition will depend upon the stage of embryo development. The actual number will vary by center and can best be calculated by using pregnancies delivered in patients using donor oocytes. The definition of RIF used in our program requires the transfer of =8, 8-cell stage embryos or =5 blastocyst embryos. Evidence of implantation is accepted when there is a rise in hCG for hCG measurements made 12 and 14 days after the hCG injection that is given to trigger the time of retrieval.