Fertility – Basic data

• Fertility and its disorders are among the most misunderstood health problems, laden with stress, anxiety, haste and prejudice. For many of us, it may be the first contact with doctors, examinations, surgeries.
• The main source of anxiety is the delusion that ‘everyone else has children easily, while we have some rare and serious problem’.
• So let’s start with a few simple facts to make it clear that fertility in general is not a simple process. It is a chain with many links and everyone must work correctly and in harmony.
• Contact must be made at the right time, around ovulation. Then the mature egg is released on the surface of the ovary and is picked up by the fallopian tubes. The fallopian tube pushes it inside. There it will meet the sperm, which in turn has passed through the vagina and uterus and from there has reached the fallopian tube. The sperm must ‘manage’ to penetrate the egg, and the fertilized embryo is formed. This should now travel halfway down the fallopian tube and settle into the uterine cavity. Implantation must occur smoothly and the embryo must grow and divide and penetrate the uterine wall. Only then will we have a positive pregnancy test.
• There are many stages and in each couple infertility may be due to a combination of ‘weak links’.
• Ovulation always occurs 14 days before the next period. Therefore, in a 27-day cycle, it occurs on the 13^th day and, in a 35-day cycle, on the 21^st day.
• Ovulation is a momentary phenomenon, when the follicle breaks and the egg is released. Then, in the next 6 hours, the fallopian tube will “grab” the egg and push it inside, where it will meet the sperm.
• The egg is therefore ‘available’ for fertilization 6 hours after ovulation and for the next 18 hours.
• Sperm survive inside the uterus and fallopian tubes for 40-80 hours after ejaculation.
• The ideal time phase for intercourse is 24 hours before until the day of ovulation, but not later because shortly after ovulation the cervical mucus becomes hostile to the sperm.
• If 1,000,000 sperm are left at the entrance to the vagina, statistically only one of them will reach the egg in the fallopian tube.
• The ideal fertility, for a young, healthy, tested couple, per month of trying is about 20%.
• After 12 months of trying, about 85% of couples will achieve conception and for the remaining 15% we are now talking about infertility.
• Fertility has always been a difficult matter, it’s just that today we are delaying having children and that adds to the burden. And if there were still problems in older generations, these women will not confide in you. All grandmothers and aunts are willing to describe setbacks in their childbirth, but none will readily admit to difficulties conceiving.
• Fertility is therefore not self-evident. It must be treated correctly and responsibly, without silly prejudices and, ultimately, without unnecessary stress, together with us at least 1 in 6 couples suffer.
• The investigation of infertility is carried out with calmness and clear step-by-step planning, starting with simple tests (ultrasound for ovulation control, sperm control) and ending with complex ones (salpingography, hysteroscopy, laparoscopy), if deemed necessary. Our goal is the early diagnosis of a problem, without particular physical, psychological and financial suffering for the couple, and the choice of the simplest treatment with realistically the greatest chances of success.

IVF-a few words about IVF

This booklet aims to answer the many expected questions about the IVF process, treatment, follow-up, possible complications, success rates, well we’ll cover almost everything. We will also discuss them in private at our meetings, it is important that you walk in the know and not be overwhelmed with reasonable questions.

Let’s start with some simple facts:

· In Europe alone 200000 IVF cycles occur each year.

· In Greece there are over 12,000 cycles, with a number of births of almost 5,000 children per year.

· With proper monitoring the procedure becomes absolutely harmless.

· Babies born after IVF are healthy.

· Not related to future maternal health problems or carcinogenesis.

When should a couple do IVF?

First of all, let’s emphasize that in vitro fertilization has strict indications and must be the last resort in the process of assisted reproduction.

Indications for IVF are:

Unexplained infertility

where all the tests are normal and we don’t find any obvious cause and the couple has already been trying for a year and a half. Simpler treatments such as insemination for at least a few cycles are often recommended. However, any advanced age of the woman and long duration of effort (more than 2 years) are burdensome and minimize the probability of success of any simpler treatment.

Fallopian tube blockage, when the fallopian tubes have been damaged by previous fallopian tube inflammation. They can no longer accept the egg from the ovary and help in fertilization and transfer of the embryo back to the uterus for implantation. There is then a risk not only of conception failing but also of the fetus being trapped in the fallopian tube (ectopic).

Endometriosis. It is a common benign condition where endometrial cells grow outside the uterus and cause foci of local inflammation, resulting in severe pain during periods and intercourse. The body mobilizes antibodies and chemicals to fight inflammation, but these harm and create a hostile environment for eggs, sperm and embryos. The treatment is the destruction of foci with diathermy in the operating room (laparoscopy), and, if further waiting does not lead to conception, in extracorporeal.

Bad sperm parameters. The ‘male factor’ is solely responsible for 30% of infertile couples and participates as part of the problem in an additional 20%. When you consider that approximately 1 in 7 couples are infertile, you realize the extent of the problem.

What are the chances of success?

This is also the order, from best to worst, in terms of chances of success. In other words, it will succeed more easily if no cause has been found (even if this worries the couple who wonders what is to blame) and clearly more difficult when the sperm presents a significant problem.

When talking about chances of success, all the details of the background come into play. The biggest role is played by the age of the woman. The average success rate of a cycle is about 30%. For a woman over 40 it is 15%, while for a 25-30 year old woman with unexplained infertility it reaches 40-45%. If there is a positive pregnancy test after IVF, there is a 20% chance of twins and a 3% chance of triplets. These apply if 3 embryos are placed inside the uterus. If 4 embryos are placed, we have 30% twins and 6% triplets. After IVF, the risk of ectopic is at least 5%, up to 20% when the fallopian tubes are not healthy.

The risk of miscarriage is slightly increased and the age of the woman plays a role here. In a 30-35 year old woman it is 25% and in a woman over 40 it is up to 40%.

How is the treatment done?

In IVF we initially give daily injections to stimulate the ovaries to produce many eggs. As these mature in the ovaries, we monitor progress with regular vaginal ultrasounds. We want enough eggs to be able to choose the best quality ones, but we must not over-stimulate the ovaries with large doses of injections.

When all the eggs are ripe, at the right time of the cycle, we do the egg retrieval. Ovulation is performed, after a short and mild general anaesthesia, with a fine needle that enters the ovaries through the vagina and aspirates the eggs. The procedure is directly controlled with a simultaneous vaginal ultrasound. As soon as the eggs are collected, they are taken to the laboratory where, under ideal conditions, they are placed together with the husband’s sperm sample. The next day the embryologist looks under the microscope how many eggs were fertilized and how many embryos we have and assesses their quality. The embryos are matured for an additional 1-2 days in the laboratory, and then the best quality embryos are placed with a thin painless catheter into the uterus, where they are allowed to implant and grow. Any embryos left over are frozen and preserved for future use. After about 2 weeks a pregnancy test is done.

What is the benefit of all this hassle?

The benefit is multiple. We achieve good stimulation of the ovaries, we get many eggs and so we have enough embryos and we can choose the best ones. Also the already ‘filtered’ and improved sperm is encouraged to fertilize the eggs in the ideal and controlled conditions of the laboratory.

In addition, if the fallopian tubes have a problem, IVF solves the problem since we collect the eggs from the ovaries and place the embryos directly in the uterus. The embryos again have the possibility to mature for two days in the excellent conditions of the laboratory, away from any harmful factors in the fallopian tube or the uterus (due to endometriosis, salpingitis, or simply old age of the woman).

Finally, frozen embryos are an additional opportunity, just as good as ‘fresh’ embryos, as long as they survive the thawing process (and they do at around 70%).

What is micro insemination (ICSI)?

When the sperm presents significant problems, there is the fear that when we place sperm and eggs together, that it will not succeed in penetrating the egg and fertilizing it and thus the next day it will be too late. In these cases, we intervene and as soon as we take the eggs, we select healthy sperm, and under the microscope, with a special needle, we pierce the wall of the egg and insert the sperm. So we are guaranteed penetration and fertilization and just wait to see the development and quality of the embryos.

Micro-fertilization is wrong to be a routine procedure. It is only required when our sperm is of particular concern. For the woman the process is the same, only the laboratory part is different. However, the know-how is more expensive and the cost increases by approximately 1000 euros. In addition, there is the theoretical concern that the sperm was the one we chose, it did not prevail over the other millions in the ‘natural selection’ of fertilization. However, all pregnancies and children born with ICSI were normal, without particular problems.

ICSI has been practiced since 1982. We just don’t know if the male children will have the same fertility problem, which will be answered soon.

What are the risks and possible complications?

The problems start when the couple and the doctor want ‘at all costs’ to achieve a positive pregnancy test. Large doses of injections without proper monitoring can lead to hyperstimulation, with many eggs, swelling of the ovaries and an insidious clinical syndrome that even threatens the life of the woman.

By the same logic, the thoughtless placement of many (more than three) embryos leads to increased multiple pregnancies and let’s not forget that triplets are an extremely dangerous pregnancy for prematurity, poor growth, brain disorders. Suffice it to say that, by law, the transfer of multiple embryos is also illegal in Greece, and the price, of course, is that the ‘success’ rates are a little worse. The middle path is also the right one, i.e. individualized treatment, objective assessment and joint decision, having weighed the pros and cons, respecting the risks and the existing legislation.

What is the cost of an IV cycle?

Roughly speaking, the total cost of a cycle (laboratory and doctor’s fee, ultrasounds, blood tests, operating room and anesthetist expenses, laboratory consumables) is 3000 euros. If micro fertilization is needed, the cost reaches 3300 euros. Of course, we also look forward to the possibility of freezing surplus embryos, thus obtaining an additional opportunity, without the same severe physical, psychological or financial costs. (Freezing and preserving the embryos for one year costs 400 euros). You adjust the financial part directly with the accounting department of the Reproduction Center.

What exactly will happen when we decide to move on?

At a final visit we will recap the history, some additional blood tests will be ordered, and I will explain the exact treatment regimen that fits your needs and history. The treatment regimen we will use is based on well-tested drugs with proven results in thousands of women in international reference centers. I will give you a multi-page personalized brochure where I will describe step by step the whole process.

Our constant contact with frequent appointments and 24-hour telephone communication will play a big role in the proper preparation for the best result. We will do all ultrasounds together, discuss progress and change medications and doses if developments require. We will not be satisfied with a routine scheme but will personalize it to your measurements with the given history and always at the given time.

In short, you will be sick of seeing me for the next few weeks. You will feel better that you will always see the same doctor you trust, who knows you and who will have the full picture but also full responsibility, and who will not let holidays and weekends threaten your treatment. It is proven that the best international results in IVF are achieved by the ‘team of three’, that is, the close bond between the couple and their doctor, away from noisy centers with many doctors and the risk of anonymity.

All this is good, but everyone tells us that we are in for a horrible experience.

Bad lies, the procedure involves drugs, injections, ultrasounds, chasing insurance funds, a surgery and statistically it is likely that it will not succeed.

It is also true that the whole experience is awful when it is accompanied by insufficient information, false hopes and unpleasant surprises, without corresponding support. My priority is for you to know all the facts without embellishments and unfounded promises and make a mature decision to move forward. Along the way, I will be there for you with constant guidance and information, and we will move forward with well-founded optimism. Extracorporeal is not a machine that grinds hopes and expectations, but a crowning achievement of scientific knowledge and the miracle of creating a new life must not be a horrible experience.