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In this comprehensive book, future parents will find up-to-date information on a wide range of familiar topics, including preconception assessment, prenatal care, recommended medical examinations, nutritional plans, and exercise guidelines for expectant mothers, among others. The book also offers detailed insights into caring for newborns and babies during their crucial first year of life.
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PROFESSIONALS WHO CONTRIBUTED TO THE CONTENT OF THIS EDITION.
Susana Aguilera P. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Verónica Álvarez V. | Physician, Nutrition, Advanced Center of Metabolic Medicine and Nutrition (CAMMYN).
Carlos Barrera H. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Eugenio Canessa B. | Physician, Anesthesiology, Department of Anesthesiology, Clínica Las Condes.
Sofía Castro L. | Clinical Lactation Specialist, Department of Pediatrics, Clínica Las Condes.
Elizabeth Chong K. | Physician, Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Clínica Las Condes.
Fanny Cortés M. | Physician, Genetics, Department of Genetics, Clínica Las Condes.
Javier A. Crosby R. | PhD, Reproductive Medicine Unit, Department of Obstetrics and Gynecology, Clínica Las Condes.
Ada Cuevas M. | Physician, Nutrition, Department of Nutrition, Advanced Center of Metabolic Medicine and Nutrition (CAMMYN), Adjunct Associate Professor, Universidad Finis Terrae.
Carlos Díaz M. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
María Jesús Estay S. | Nutritionist, Advanced Center of Metabolic Medicine and Nutrition (CAMMYN).
Cecilia Fabres V. | Physician, Reproductive Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Emilio Fernández O. | Physician, Reproductive Medicine, Department of Obstetrics and Gynecology, Clinica las Condes
Alfredo Germain A. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Jorge Gigoux M. | Physician, Anesthesiology, Department of Anesthesiology, Clínica Alemana.
Rogelio González P. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Miguel Guelfand C. | Physician, Pediatric and Neonatal Surgery, Department of Pediatric Surgery, Clínica Las Condes.
Enrique Guiloff F. | Physician, Department of Obstetrics and Gynecology, Clínica Las Condes.
Paula Gutiérrez M. | Midwife.
Stefan Hosiasson S. | Physician, Neonatology, Department of Pediatrics, Clínica Las Condes.
Enrique Jadresic M. | Physician, Psychiatry, Associate Professor at the University of Chile.
Catalina Larraín F. | Psychologist, Maternal-Infant and Perinatal Mental Health, Cryas Team.
Juan Luis Leiva B. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Marcela Moyano O. | Midwife, Clínica Las Condes.
Hernán Muñoz S. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Mauricio Pinto C. | Physician, Neonatology, Department of Pediatrics, Clínica Las Condes.
Andrés Pons G. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Lorena Quiroz V. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Gustavo Rencoret P. | Physician, Maternal-Fetal Medicine, Clínica Alemana.
Jorge Andrés Robert S. | Physician, Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Clínica Las Condes.
Maureen Rossel G. | Physician, Pediatrics, Department of Pediatrics, Clínica Las Condes.
Marta Sánchez M. | Nurse-Midwife, Clínica Alemana.
Eduardo Sepúlveda | Physician, Maternal-Fetal Medicine, Clínica Alemana
Jennifer Silva R. | Clinical Lactation Specialist, Department of Pediatrics, Clínica Las Condes.
Mariana Valenzuela Cruz. | Lawyer, Council for the Defense of the State.
Hernán Villalón U. | Physician, Neonatology, Department of Pediatrics, Clínica Las Condes.
Constanza Von Dessauer G. | Psychologist, Doula.
ALFREDO MANUEL GERMAIN ARAVENA
Graduated with a degree in Medicine from the University of Chile and completed his studies in Obstetrics and Gynecology at the Pontifical Catholic University of Chile. He further pursued a postgraduate program in Maternal-Fetal Medicine at the University of Texas, Southwestern Medical Center in Dallas, United States.
Between 1986 and 2004, he served as a Professor in the Department of Obstetrics and Gynecology at the Pontifical Catholic University of Chile, specializing in Maternal-Fetal Medicine and dedicating his efforts to preventing and treating medical problems related to pregnancy. He is recognized for his contributions through numerous publications in basic and clinical research in complex pregnancies.
In 2004, he founded the Maternal-Fetal Surveillance Specialized Center (CEVIM) at Clínica Las Condes, where he held the director position for 8 years. Alfredo is an esteemed member of the certification panel for the sub-specialty of Maternal-Fetal Medicine of CONACEM. He actively participates in major Chilean and American societies related to Obstetrics, Gynecology, and Maternal-Fetal Medicine. Additionally, he remains an integral part of the Maternal-Fetal Medicine Unit in the Department of Obstetrics and Gynecology at Clínica Las Condes.
Alfredo's passion lies in focusing on preventing, caring, and treating pregnancies with difficulties, making a significant impact in the field of Maternal-Fetal Medicine.
Content
Prologue
| Aníbal Llanos M. | María J. Serón - Ferré |
Presentation
| Alfredo Germain A. |
1. Pregnancy: How and When
| Cecilia Fabres V. | Emilio Fernández O. | Javier A. Crosby R. | Alfredo Germain A. |
2. Preconception Assessment
| Alfredo Germain A. | Gustavo Rencoret P. | Rogelio González P. |
3. What to do After Confirming Pregnancy
| Alfredo Germain A. | Marta Sánchez M. | Hernán Muñoz S. | Carlos Díaz M. |
| Rogelio González P. |
4. Fetal Development
| Alfredo Germain A. | Marta Sánchez M. | Juan Luis Leiva B. |
| Rogelio González P. |
5. Ultrasounds During Pregnancy
| Alfredo Germain A. | Carlos Díaz M. | Hernán Muñoz S. | Rogelio González P. |
6. Structural Analysis in Newborns – A Guide on What to Do
| Fanny Cortés M. | Susana Aguilera P. | Alfredo Germain A. |
7. Fetal Assessment and Therapy
| Hernán Muñoz S. | Alfredo Germain A. | Carlos Barrera H. | Carlos Díaz M. |
8. Twin and Multiple Pregnancy
| Susana Aguilera P. | Alfredo Germain A. |
9. Changes and Maternal Care During Pregnancy
| Alfredo Germain A. | Susana Aguilera P. | Hernán Muñoz S. |
10. Mental Health During Pregnancy
| Catalina Larraín F. | Alfredo Germain A. | Enrique Jadresic M. |
11. Legal Aspects of Pregnancy
| Mariana Valenzuela C. | Paula Gutiérrez M. | Marta Sánchez M. | Marcela Moyano O. |
12. Eating Habits During Pregnancy
| Ada Cuevas M. | Verónica Álvarez V. | María Jesús Estay S. |
13. Physical Activity During Pregnancy
| Carlos Díaz M. | Alfredo Germain A. | María Jesús Estay S. |
14. Complex Pregnancies
| Alfredo Germain A. | Juan Luis Leiva B. | Andrés Pons G. | Rogelio González P. |
15. Preparing for Delivery
| Alfredo Germain A. | Marcela Moyano O. |
16. Anesthesia During Labor
| Eugenio Canessa B. | Jorge Gigoux M. |
17. The Moment of Childbirth
| Alfredo Germain A. | Jorge Andrés Robert S. | Eduardo Sepúlveda S. |
18. The Doula: a New Partner
| Constanza Von Dessauer G. | Alfredo Germain A. |
19. The First Days of Life of the Newborn
| Stefan Hosiasson S. | Catalina Larraín F. | Hernán Villalón U. |
Mauricio Pinto C. |
20. Neonatal Surgery
| Miguel Guelfand C. |
21. Newborn Care at Home
| Hernán Villalón U. | Stefan Hosiasson S. | Mauricio Pinto C. |
22. Breastfeeding
| Maureen Rossel G. | Elizabeth Chong K. | Sofía Castro L. | Jennifer Silva R. |
23. Postpartum: Adapting to Motherhood
| Alfredo Germain A. | Enrique Jadresic M. | Marcela Moyano O. |
24. The Newborn’s First Year of Life
| Hernán Villalón U. | Stefan Hosiasson S. | Enrique Jadresic M. |
25. Myths of Pregnancy and Childbirth
| Enrique Guiloff F. | Marta Sánchez M. |
26. Responsible Parenthood and Fertility Regulation
| Lorena Quiroz V. | Alfredo Germain A. |
27. Choosing the Baby's Name
| Alfredo Germain A. | Marta Sánchez M. |
Glossary
| Alfredo Germain A. |
Prologue
Composing this Prologue, which we could call "variations for keyboard with four hands on a work by Alfredo Germain Aravena," is a great privilege. The performers, María Serón - Ferré and Aníbal Llanos Mansilla, wholeheartedly commit to bearing witness to some of Alfredo's knowledge adventures and his latest work, a new book.
First movement: Ephemeral youth. We knew him as a 2nd-year medical student and later as a Student Assistant for the following 5 years. He proved to be one of the most productive researchers in the laboratory, studying cardio-respiratory responses to fetal oxygen deficiency. Even back then, he displayed a gift for writing, being the author and co-author of several published works. With many attributes, he transformed from a timid start to becoming a dedicated, inquisitive, and involved student. Upon graduating, he earned a scholarship in Obstetrics and Gynecology at the Pontifical Catholic University, initiating a collaboration with Dr. María Serón.
Second movement: The age of reason. From the dedicated, inquisitive, and involved student emerged a comprehensive academician who combined active teaching and clinical work with significant contributions to knowledge through various publications cited worldwide. Without abandoning these pursuits and paraphrasing Nicanor Parra, Germain stepped down from Olympus and wrote about a subject immortalized by Leonardo da Vinci with "La Gioconda," which masterfully portrays the phenomenology of a pregnant woman, the paradox of the enigmatic smile alongside the beatitude in her bodily expression. Thus, Alfredo and a select group of collaborators wrote "Embarazo y Recién Nacido. Guía para futuros padres," an extraordinary and much-needed book.
Third movement: The current work, "Embarazo: antes, durante y después. Todo lo que los futuros padres deben saber." Over the years, Alfredo maintains his spirit and graciously transfers his knowledge and that of his collaborators to his readers, accompanying them like an expert sherpa through one of the most mysterious and profound journeys of our species: the creation of a new human being. Quoting Jacques L. Monod, Nobel Prize in Medicine, "A dream written n our genes." This edition, from the very first chapter, updates and expands on the topics covered in previous editions, incorporating others such as assisted fertilization, support during gestation, and contemporary approaches to genetic problems. This is a formidable work, a comprehensive vision of a complex biological process useful not only for mothers and fathers but also, as predicted by Dr. Wild in the prologue of Germain's first book, "a work for students and academia." Undoubtedly, a necessary opus to keep at hand.
DRA. MARÍA J. SERÓN - FERRÉ
Physiology Professor
Pontifical Catholic University of Chile
DR. ANÍBAL LLANOS MANSILLA
Pathophysiology Professor and Pediatrician
University of Chile
Presentation
Before you were conceived
You were desired
Before you were born
You were already loved
Even an hour before you were here
I would have given my life for you
This is the miracle of life
MAUREEN HAWKINS, "THE MIRACLE."
The intrauterine period plays a vital role in shaping our lives. Most of a person's characteristics, from food preferences to language sounds and even the predisposition to certain chronic diseases, originate during our time in the mother's womb. This has transformed what was once considered a mystery into a profoundly meaningful period.
In recent years, there has been an unprecedented expansion in our understanding of the reproductive process. This has significantly impacted the development of assisted reproduction techniques and the comprehension, prevention, and treatment of pregnancy-related diseases. Today, motherhood can happen in previously unthinkable situations, such as in individuals born without a uterus, who can now experience motherhood through a uterine transplant. Moreover, genetic diagnosis of embryos at a preimplantation stage has become possible, and advances in preventing fetal diseases and genetic treatments have brought this once distant and mysterious period closer and more illuminated, fostering a strong connection and affectionate interaction between parents, the medical team, and the unborn child.
Thanks to advances in diagnostic imaging, we can now see and appreciate the unborn child from as early as 25 days post-conception. This closeness allows the child to become a part of the family life early. It is a marvel to witness this once-unreachable process, which, in my opinion, is unparalleled in the history of prenatal care.
Twenty years ago, I wrote the first version of this book in collaboration with a dear friend and an excellent healthcare professional. The book was updated in 2012 and 2018, enabling me to share my experience on pregnancy and newborn care with parents. It aimed to provide a simple, clear, updated, and detailed understanding of these topics. The acceptance and demand for this idea were gratifying, with multiple reprints and thousands of copies reaching families.
Technological advancements in diagnostic evaluation and treatment for both mothers and babies have been significant in recent years. Alongside the increasing desire for patient information, I created this new text, nearly doubling the previous editions' length. It comprehensively and clearly, covers everything necessary to know before, during, and after pregnancy.
The chapters have been written by professionals who have worked together for several years. They are esteemed in the country and have kindly supported me in this task. In addition to being gynecologists, some of them are close collaborators, friends, and specialists in Maternal-Fetal Medicine. Together, we form the most extensive team in the country in this subspecialty.
This edition marks a significant change as the text, now updated in nearly all chapters, is available in Spanish and English. It can be acquired in the traditional printed format upon request and is also available in a user-friendly electronic format accessible on all platforms and electronic libraries worldwide. This accessibility allows sharing this text with approximately 1.9 billion Spanish and English speakers—a dream come true.
I sincerely thank those who have made this new book version possible. Firstly, to the Chilean Atherosclerosis Working Group corporation, for their support in preparing and disseminating this book. Secondly, to the Chilean Society of Obstetrics and Gynecology (SOCHOG), who have supported this project for the past 15 years. Their endorsement again places this book among the few on this topic worldwide and the only one in Chile with the backing of the respective Medical Society.
A special mention goes to my family for their understanding and support during the time dedicated to this project.
Lastly, I express my heartfelt thanks to all my patients and their families, who have entrusted me with their medical care during one of the most significant periods of human life: the arrival of a child.
ALFREDO GERMAIN ARAVENA
Gynecologist-Obstetrician / Maternal-Fetal Medicine
Clínica Las Condes
1.
Pregnancy: How and When
| Cecilia Fabres V. | Emilio Fernández O. | Javier A. Crosby R. | Alfredo Germain A. |
HAVING A CHILD: A TURNING POINT
Becoming parents is one of the most significant events in a couple's married life. The arrival of a child to the family is a couple's decision, but above all, it is a gift that changes their lives forever. In this context, children are unique, unrepeatable, independent persons who should be expected with love, welcomed, and respected from the onset of pregnancy.
To ensure a pleasant experience, future parents should visit their doctor to confirm their suitable physical condition and, if necessary, make lifestyle changes that can contribute to a normal pregnancy.
FINDING THE RIGHT TIME
Determining the most appropriate time for pregnancy can be challenging. The childbearing age for women ranges from 15 to 42 years old. However, it is crucial to balance age, health, emotional and work conditions, and the couple's situation. The decision should be mutual. Ideally, women should aim to have their first pregnancy between 25 and 35 years old. Delaying the decision for too long can make conception increasingly tricky, especially after age 38, when the rate of spontaneous abortions rises due to chromosomal abnormalities in the ova. Typically, a healthy couple in which the woman is under 35 years old and has an active sexual life has an 80% chance of pregnancy within a year without using fertility methods. This probability increases to 90% after two years. However, this period decreases to 6 months for women over 35. It is recommended for couples who have been actively trying to conceive for 12 months without success to undergo a medical evaluation, as it is considered "infertility" after that period. There are various situations in which it could be beneficial to consider the appropriateness of getting pregnant. Here are some examples.
DOES THE PARENT'S AGE MAKE A BIG DIFFERENCE?
While technology offers ways to achieve pregnancy at later maternal and paternal ages, it is crucial to understand the biological limitations involved. For women, the efficiency of the reproductive process declines after age 35 due to the quality of the oocytes. Fertility decreases spontaneously, and the frequency of miscarriages increases from 20% at age 35 to 50% at 40 and 90% at 45. The global risk of chromosomal abnormalities at these ages is 1/92, 1/66, and 1/21, respectively. Moreover, advanced maternal age is associated with a higher likelihood of developing adverse health conditions during pregnancy, such as high blood pressure and diabetes mellitus. However, with proper medical care from specialists in Maternal-Fetal Medicine, successful pregnancies can be achieved in most cases. As for the father, the risk of infertility doubles at age 40, and there is an increased risk of early miscarriage and premature labor. Research also suggests a correlation between fathers aged 50 and certain rare health conditions in newborns, including congenital syndromes, bone development abnormalities (achondroplasia and osteogenesis imperfecta), and neurologic development alterations such as autism spectrum disorders. Fortunately, modern embryo analysis technology detects many complications, especially chromosomal abnormalities, before implantation. We will delve into this topic further in this chapter. In summary, while achieving a successful pregnancy later in life is possible, it should be a carefully considered decision supported by a medical team who can provide advice on effective measures to ensure a joyful and medically safe experience for both the mother and the baby.
WHAT IS THE RECOMMENDED TIMEFRAME BETWEEN PREGNANCIES?
Several factors influence this decision, but waiting at least 12 months between one pregnancy and the next is advisable. This interval allows the mother to fully recover physically and mentally from the demands of breastfeeding and caring for a child.
HOW LONG SHOULD A WOMAN WAIT AFTER A CESAREAN SECTION?
Recovering from a cesarean delivery, an abdominal surgery, requires ample time for proper healing. It is advisable to wait at least 12 months, or potentially longer, depending on the number of previous c-sections.
HOW LONG SHOULD A WOMAN WAIT AFTER A MISCARRIAGE?
It is common for women to conceive in the menstrual cycle immediately following a miscarriage. However, most obstetricians recommend waiting for at least two menstrual cycles before attempting to conceive again.
In cases of frequent miscarriages (two or more consecutive losses), it is advisable to undergo further medical evaluations before considering another pregnancy.
HOW LONG SHOULD A WOMAN WAIT AFTER BEING VACCINATED AGAINST MEASLES?
Before attempting to conceive, it is crucial to verify immunity against measles through IgG (indicating immunity) and IgM (indicating recent infection) antibody tests. If both tests yield negative results, it is recommended that the mother-to-be receive the measles vaccine.
After vaccination, it takes approximately three months to develop immunity against the disease. Hence, during this period, the woman must avoid measles exposure and postpone pregnancy. If she is already pregnant, it is advised to delay vaccination until after childbirth while taking precautions to prevent measles infection.
HOW TO CONCEIVE
FEMALE REPRODUCTIVE SYSTEM
The female genital system consists of both internal and external parts. The external part includes the labia majora, labia minora, and clitoris, while the internal part comprises the vagina, uterus, fallopian tubes, and ovaries.
The vagina, approximately 7.5 cm long, is a tubular organ composed of elastic fibromuscular tissue covered by pluristratified epithelium. It responds to ovarian hormones, specifically estradiol and progesterone. Besides facilitating sexual intercourse and acting as the receptacle for seminal fluid, the vagina also serves as the birth canal through which a baby is delivered during normal or vaginal childbirth. At the end of the vagina is the uterine neck.
The uterus is a muscular organ with two parts: the cervix and the uterine corpus. Made of stretchable smooth muscle fibers, it can expand and accommodate the growing fetus during pregnancy. The uterus provides a sufficient blood supply to the placenta through uterine arteries, nourishing the developing pregnancy. During labor, it contracts to enable cervical dilation and facilitate childbirth.
The ovaries on each side of the uterus and connected to the distal end of the fallopian tubes serve as the female gonads. They contain ova and female gametes. Within the ovaries, follicles develop and mature, releasing a mature egg during each menstrual cycle. This egg is fertilized and implanted in the uterus, initiating pregnancy or released unfertilized.
THE OVARIAN CYCLE OR MENSTRUAL CYCLE
The menstrual cycle typically lasts between 28 and 30 days. During this cycle, the pituitary gland stimulates the ovaries through the Gonadotropin hormone, aiding in the development, maturation, and release of an egg from the ovary around day 14, known as "ovulation." Throughout the egg's growth and maturation, estrogen levels increase. Estrogen is necessary to produce cervical mucus and the thickening of endometrial glands, which support embryo development.
After leaving the ovary, the egg remains within the fallopian tube for approximately 24 hours, ready for fertilization. If fertilization occurs, the embryo starts to develop and migrates towards the uterus, a journey that takes about 5 to 6 days. As a blastocyst, the embryo reaches the uterus and remains free to move within the cavity for approximately 24 hours until it implants itself in the uterine endometrium. Tissues then start forming, giving rise to membranes surrounding the embryo and forming the placenta. The pregnancy is established through implantation.
The placenta, an organ developed from the outermost embryo layers, plays multiple crucial roles in pregnancy. It produces various hormones necessary for the baby's growth and development and facilitates the exchange of oxygen and nutrients between mother and child.
THE MALE REPRODUCTIVE SYSTEM
The male genital system consists of both external and internal parts. The external part includes the penis and the testicles covered by the scrotum. The internal part comprises the vas deferens, seminal vesicles, prostate, and urethra.
Sperm cells, formed in the testicles, travel through the epididymides and the vas deferens to reach the seminal vesicles and prostate. Seminal fluid, produced by these glands, is added to the sperm.
During intercourse, ejaculation expels semen through the ejaculatory ducts, reaching the urethra within the penis for external release.
ESTABLISHING PREGNANCY
Once in the vagina, sperm cells can survive and remain active for several hours, even days, with the help of cervical mucus. Cervical mucus is a transparent fluid produced by the cervical glands in the uterine neck, influenced by the action of ovarian estrogen. It reaches its peak before ovulation when women are most fertile.
When a sperm cell successfully penetrates the wall of an egg, fertilization occurs in the distal segment of the fallopian tube. The tube then facilitates the movement of the embryo through rhythmic movements on the surface of its cells, aided by cilia. The nuclei of the sperm cell and egg, known as pronuclei, interact and fuse, sharing the genetic information of both parents. This marks the beginning of embryo development, which involves cell division and takes 5 to 6 days until the embryo reaches the uterus, where it typically implants and initiates pregnancy.
In cases where the embryo implants in the fallopian tube instead of the uterine cavity, it is referred to as an ectopic or tubal pregnancy. Early diagnosis of this significant complication is crucial, as it can harm the mother's health. Ectopic pregnancies are not viable.
WHAT IF CONCEPTION IS NOT POSSIBLE?
If a woman cannot conceive after 12 months of regular sexual activity (2 to 3 times a week), it is advisable to seek a medical diagnosis to determine the underlying cause. However, it is now possible to address and resolve the issue in most cases.
Infertility can be categorized as primary, when a couple has never been able to conceive, or secondary, when they have previously had a child but cannot have another. The causes of infertility can stem from either the woman or the man, and sometimes both. Approximately 30% of infertility cases are attributed to male factors, another 30% to female factors, and around 30% to a combination of both. The remaining 10% of patients have unknown causes.
MALE INFERTILITY
1. CAUSES RELATED TO ABNORMALITIES OF SPERM CELLS OR MALE GAMETES, EITHER IN:
›Production
›Release
›Morphological Characteristics
›Functional Characteristics
The initial assessment involves analyzing a semen sample to evaluate various aspects, including the concentration of sperm cells, their progressive mobility, vitality, and the characteristics of the seminal fluid. This examination also considers factors such as the presence of round cells, debris, antibodies, and other relevant indicators.
2. MALE CAUSES ASSOCIATED WITH OTHER FACTORS
›Infectious Factors
›Inflammatory/Vascular Factors, such as Varicocele
›Hormonal Factors
These conditions can often be effectively treated with a range of interventions, including antibiotics, anti-inflammatory drugs, vitamins, hormones, and, in some cases, surgery. However, it's important to note that certain conditions currently lack effective treatment options. Fortunately, advancements in assisted reproductive techniques (ARTs) offer hope to couples facing such challenges. Sophisticated and complex procedures, such as insemination, bypass, and methods like In vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), enable many couples to achieve pregnancy and fulfill their dream of having a child, even in the presence of these conditions.
3. DONATION OF SPERM CELLS
Sperm cell donation is recommended for men who do not produce sperm or have low-quality sperm cells that cannot fertilize oocytes, even with techniques like IVF or ICSI. It is also used in cases where men have a hereditary disease that could potentially impact the quality of life in their offspring or make conception impossible.
In such situations, the complexity of the treatment for the male partner does not necessarily reflect the complexity of the woman's treatment, particularly if she is healthy. Ovulation stimulation can be achieved through echography monitoring to identify the fertile period when she can be inseminated with the donated sample.
FEMALE INFERTILITY
1. OVULATORY FACTOR OR GONADAL ENDOCRINE: Causes related to developmental abnormalities and maturation of oocytes.
The ovulatory factor is connected to the functionality of the ovary. As the ovary is a gland of the endocrine system, regulated by the pituitary gland, a well-balanced female endocrine system is essential for its proper functioning. Therefore, women can experience ovulation disorders if their thyroid or adrenal glands malfunction.
The ovary serves two primary functions:
›Maturing and releasing an oocyte in every menstrual cycle is known as ovulation.
›Producing and secreting hormones that support pregnancy and other tissues is called the endocrine function.
Both functions are interdependent, meaning that if one fails, it can affect the other.
Today, accurate assessment of ovarian function is possible through an ovulation study, which involves echographic monitoring of the developing follicle and measuring specific hormones in the blood to identify any disorders and address them appropriately. Additionally, the quality of the endometrium's thickening and characteristics and the quality of cervical mucus can be evaluated throughout the cycle.
These analyses help identify the underlying causes and guide the treatment options. Depending on the specific alterations observed, the treatment may involve correcting ovulation or restoring general hormonal function. The medical team discusses various options with the patient, ranging from dietary changes to medication use.
Different methods exist to correct the ovulatory factor, and numerous drugs are available to stimulate ovulation. Selecting the most suitable treatment depends on the patient's diagnosis and individual characteristics. Typically, treatment begins with non-invasive and cost-friendly oral medications. However, injectable drugs can also be considered if the patient does not respond favorably or the diagnosis necessitates it.
The most common procedure involves conducting 3 to 5 cycles of ovulation stimulation, with echographic monitoring, to identify the fertile period and indicate the timing of intercourse. Before starting stimulation, it is recommended to perform an x-ray of the uterus and tubes (hysterosalpingography, HSG). In some cases, a procedure known as intrauterine insemination (IUI) or "bypass" may be performed. If pregnancy is not achieved after this initial "low complexity" treatment, the doctor may proceed with further tests such as endometrial biopsy, immunological exams, laparoscopy, or hysteroscopy. These surgical procedures can diagnose and correct conditions such as endometriosis, a secondary adherence syndrome caused by inflammation, myomas, polyps, and other factors.
While medical records or ultrasound findings can suggest some of these conditions, laparoscopy is required for accurate diagnosis and correction.
Once the correct diagnosis has been made and all the factors have been addressed, and if the "desired pregnancy" has not been achieved after completing the low-complexity treatment stage, it is time to consider high-complexity treatments or Assisted Reproductive Techniques (ARTs).
The timing of when a doctor offers this type of treatment to a couple depends on several factors, with the woman's age, duration of infertility, ovarian reserve, previous surgery records, and associated male factors being among the most important considerations.
2. OVARIAN RESERVE
Ovarian reserve refers to the number of follicles or eggs a woman has at a specific time. It is highest at birth and gradually declines over time through a natural biological process called atresia or programmed cell death and through successive ovulations throughout a woman's life, starting from menarche or the first menstruation.
At birth, a baby girl typically has around 500 to 800 thousand follicles or ova in both ovaries, but by menarche, this number decreases to around 200 to 250 thousand. The ovarian reserve continues to decrease progressively until menopause.
The ovarian reserve can be measured or estimated by assessing the plasma levels of Anti-Mullerian Hormone (AMH), which is produced by the ovarian follicles, or by counting the Antral Follicles in both ovaries through transvaginal ultrasound during the early days of the menstrual cycle (around day 2-3), along with the measurement of FSH and Estradiol.
Some studies suggest that the rate of follicle loss accelerates around the age of 36-37. Other factors can also contribute to a decreased ovarian reserve, such as extensive ovarian surgery (due to endometriosis or ovarian cysts), certain autoimmune diseases affecting the ovaries, or exposure to toxic agents or radio/chemotherapy treatments.
When the ovarian reserve is low, particularly in older women, achieving spontaneous pregnancy becomes more challenging, and there is an increased risk of miscarriage due to the decreased quantity and quality of oocytes. However, in young women with low ovarian reserve resulting from extensive surgery where only a portion of the ovarian tissue is removed, the number of oocytes may be decreased while preserving their quality relative to the woman's age, leading to a better reproductive prognosis.
On the other hand, women with Polycystic Ovary Syndrome (PCOS) are born with a higher number of follicles or ova, resulting in a greater ovarian reserve compared to individuals of the same age without this condition.
Various treatment strategies are currently available to address decreased ovarian reserve. One such approach involves supplementation with different combinations of vitamins/antioxidants, which has shown promising results in improving the quality of oocytes obtained through in vitro fertilization procedures. Another experimental technique being explored is injecting stem cells or culture medium directly into the ovaries, aiming to promote the rejuvenation of the remaining follicles. These innovative methods hold potential for enhancing ovarian function and optimizing fertility outcomes. However, further research is required to fully understand these approaches' efficacy and safety.
3. TUBOPERITONEAL FACTOR: Causes related to abnormal transport of sperm cells to the distal portion of the tubes and the fertilized oocyte to the uterine cavity.
The tuboperitoneal factor may be suspected if there is a history of pelvic inflammatory/infectious disease or abdominal conditions (such as severe appendicitis, peritonitis, or adnexitis), as well as prior use of intrauterine devices or uterine/tubal surgeries (such as curettages or previous ectopic pregnancy). The presumptive diagnosis is typically conducted using a radiologic exam called hysterosalpingography (HSG), where X-ray images of the tubes and uterus are taken. At the same time, a water-soluble radiopaque contrast medium is introduced through the uterine cervix. Another diagnostic method involves a thin tube inserted through the navel to directly observe the pelvic organs (laparoscopy) or an ultrasound exam where a physiological solution is administered through the cervix to assess the shape of the uterine cavity and fallopian tube permeability.
4. UTERINE FACTOR: Causes related to abnormalities or anatomical defects of the uterine cavity.
Uterine abnormalities can be either congenital (complete or incomplete walls) or acquired diseases of the uterine wall, such as myomas, or abnormalities in endometrial thickness (pathological reduction) that can result in adhesions or pathological thickening, such as endometrial hyperplasia or polyps. Uterine abnormalities can be diagnosed through a transvaginal ultrasound, but confirmation and treatment are typically performed using hysteroscopy. During hysteroscopy, a thin tube called a hysteroscope is inserted through the cervical canal to visualize and treat any surface abnormalities within the uterine cavity..
5. CERVICAL FACTOR: Causes related to abnormalities of the uterine neck that can be anatomical or inflammatory.
The cervical factor refers to the disturbance in the normal function of the uterine cervix. The cervix acts as a barrier that sperm cells must cross to reach the oocytes, and it produces cervical mucus that aids in sperm transport during different phases of the menstrual cycle. Various factors can contribute to cervical factor infertility, including cervical infections, birth traumas, previous surgeries, or antisperm antibodies in the cervical mucus. In many cases, this issue can be resolved; otherwise, intrauterine insemination (IUI) can be utilized. During IUI, selected sperm cells from the partner or donor are placed directly into the uterine cavity using a thin catheter. The sperm cells used in IUI are carefully chosen based on quality and mobility through laboratory procedures.
6. PELVIC ENDOMETRIOSIS
Pelvic endometriosis has an estimated incidence of 40% among infertile women. It should be suspected in cases of dysmenorrhea or severe and progressive menstrual pain that is not alleviated with typical painkillers. Symptoms such as dyspareunia (painful intercourse) or chronic pelvic pain have also been associated with endometriosis. This condition can be diagnosed through laparoscopy, ultrasound, or pelvic magnetic resonance imaging. Persistent ovarian cysts with a finely granulated or lumpy appearance may indicate endometriosis. Endosonography can also be used for diagnosis. Laparoscopic surgery is the primary treatment for endometriosis. When all existing endometriosis lesions are successfully removed through surgery, the fertility prognosis is favorable, with approximately half of the patients achieving pregnancy within six months following the procedure.
HIGH-COMPLEXITY REPRODUCTIVE MEDICINE
Assisted Reproductive Treatments (ARTs) are advanced techniques in reproductive medicine that involve the manipulation of oocytes, sperm cells, or human embryos in laboratory settings to facilitate pregnancy.
The Assisted Reproductive Techniques used today are:
1.In Vitro Fertilization: IVF
2.Intracytoplasmic Sperm Injection: ICSI
3.Embryos or Blastocyst Vitrification
4.Oocytes vitrification to preserve fertility.
5.Egg Donation/Embryo Donation/Sperm Cells Donation
6.Preimplantation Genetic Diagnosis: PGD
MOST COMMON INDICATIONS OF ASSISTED REPRODUCTIVE TECHNIQUES (ARTs)
Assisted reproductive techniques are recommended in the following scenarios:
·Couples who have undergone thorough diagnostic evaluations, addressed and corrected potential causes of infertility, and completed appropriate low-complexity treatments have not achieved pregnancy.
·Couples where the woman either lacks fallopian tubes or has structural abnormalities in the tubes.
·Couples where the woman exhibits diminished ovarian reserve or is over 37-38 years old.
·Couples experiencing unexplained infertility, a condition categorized as such by the International Classification of Diseases (ICD).
·Male factor infertility, wherein issues related to sperm quality, quantity, or function are present.
·Cases involving mild to moderate endometriosis that have necessitated extensive surgical intervention.
·Couples who have been struggling with infertility for a duration exceeding five years.
·These indications warrant the consideration and implementation of assisted reproductive techniques, offering hopeful prospects for individuals and couples seeking to overcome their fertility challenges and achieve the cherished goal of pregnancy.
1. IN VITRO FERTILIZATION AND EMBRYO TRANSFER (IVF/ET)
In Vitro Fertilization and Embryo Transfer (IVF/ET) is an assisted reproductive technique tailored to help couples experiencing infertility. It provides a solution when sperm cells cannot naturally fertilize ova within the fallopian tube. This remarkable procedure occurs within a laboratory's controlled confines, facilitating the union of ova and sperm cells.
Under meticulously controlled environmental conditions encompassing factors such as pH, temperature, humidity, oxygen concentration, and carbon dioxide, ova, and sperm cells are nurtured within a specialized capsule immersed in a culture medium. This medium emulates the composition of tubal fluid, serving as a conducive environment for fertilization.
These precious embryos are judiciously transferred to the woman's uterus upon successful fertilization and subsequent embryo development. In certain instances, they may also be introduced into the fallopian tube, allowing further growth until they reach the stage at which they can firmly implant into the endometrium—the crucial internal lining of the uterus.
IVF/ET stages are:
›Ovulation Stimulation
›Follicular Suction
›Fertilization and Embryologic Development
›Embryo Transfer
a. Ovulation Stimulation
During a spontaneous ovulatory cycle, numerous follicles (ovarian structures that support oocytes) initiate their monthly development, with approximately 10 follicles in total. However, only one follicle reaches maturity, known as the dominant follicle. The remaining follicles are naturally reabsorbed and go unused by the ovary. This biological process, referred to as atresia or programmed cellular death, restricts fertilization to a single oocyte per cycle. Rarely, in extraordinary circumstances, more than one follicle is selected, resulting in the spontaneous conception of non-identical twins (occurring in approximately 1 in 95-100 births).
Ovulation stimulation is employed to recruit multiple oocytes from both ovaries, preventing the reabsorption or atresia of the follicle population alongside the dominant follicle. This approach enables more oocytes to be obtained through aspiration from the ovary, which are subsequently inseminated for fertilization.
Why is the collection of more than one oocyte necessary?
Depending on the woman's age, some eggs may have chromosomal abnormalities that can hinder fertilization or impede the normal development of the embryo and its subsequent implantation. In some cases, the embryo may successfully implant but later results in a spontaneous miscarriage, which is a natural part of the selection process. For instance, not all embryos with Down syndrome or Trisomy 21 can implant, but some manage to be born.
The likelihood of chromosomal abnormalities increases as the woman ages, reaching 70-80% of eggs in women aged 40 or above. Considering that not all obtained eggs will be mature and capable of being fertilized, not all fertilized eggs will develop into embryos, and not all embryos will successfully implant, the aim is to obtain a larger quantity of eggs.
Moreover, fertilizing more than one egg increases the probability of having multiple embryos available for transfer, increasing the chances of multiple pregnancies. The number of embryos transferred must be limited to prevent this outcome. Currently, in women under 35 years old, only one embryo (blastocyst) is typically transferred. For older women, the decision is made on a case-by-case basis. Embryos that are not transferred are frozen using vitrification or cryopreservation, allowing them to be used to achieve another pregnancy in the future.
Stimulation method in patients with normal ovarian reserve:
Every patient entering the Assisted Fertilization Program (AFP) will receive a daily dosage of at least 1 mg of folic acid medication. Some patients may require a higher dosage depending on their age and diagnosis.
To stimulate ovulation and obtain a higher number of oocytes, the process begins on the second day of a spontaneous or induced menstrual cycle using highly purified hormones administered through daily subcutaneous injections. These hormones are carefully designed to closely resemble the ones naturally produced by the pituitary gland.
The hormone options include recombinant FSH (Gonal-f or Puregon®) or a combination of FSH and LH (Menopur®, Pergoveris®). Additionally, oral medications such as Femara® or Clomiphene® may be prescribed. Thus, there are several approaches to tailor the ovulation stimulation to each patient's specific needs. An injectable medication like Orgalutren® or Cetrotide® might also be included depending on various factors. Introducing preimplantation embryo analysis allows couples to reduce the number of embryos transferred.
Occasionally, the medications used may cause mild side effects such as headaches, mood swings, abdominal bloating, or gradual weight gain. However, if symptoms such as blurred vision, severe headaches, rapid weight gain, difficulty breathing, or chest pain occur, it is crucial to inform your doctor promptly. These occurrences are infrequent, affecting less than 1% of cases.
The ovulation stimulation process typically lasts around 10 to 12 days. During this period, regular transvaginal ultrasounds are performed every other day or every two days to monitor the growth and development of the follicles. Concurrently, blood samples are taken without fasting to measure estradiol levels, a hormone the developing follicles produces, which increases as the follicles mature.
Once a significant portion of the follicles, 40-50% of them, have reached an average size of 18-20 millimeters, a hormone called hCG is administered. This hormone is responsible for finalizing the maturation of the oocytes. It is also necessary for the endometrium to have achieved an appropriate thickness, and for estradiol levels to have exponentially increased over 5-6 days. The follicular aspiration and oocyte retrieval procedure is scheduled for 36 hours after the hCG injection.
b. Follicular aspiration
Follicular aspiration is a procedure to extract the oocytes from within the ovarian follicles. It is performed in an operating room, using a needle inserted through the vagina and attached to the vaginal transducer of the ultrasound machine.
Ovarian puncture is guided using ultrasound visualization. It's an outpatient procedure that requires analgesia or sedation. The follicles in both ovaries are punctured to retrieve all the oocytes.
Before the procedure, the patient must be admitted to the hospital after fasting for at least 6 hours.
Right after the oocytes are collected, they are classified based on their morphological maturity in the laboratory. They are then stored in an incubator in labeled capsules filled with culture medium. The follicular aspiration typically takes around 30 minutes, and afterward, the patient rests in a recovery room for approximately 1 hour, depending on any potential procedure-related difficulties.
The woman's partner can bring a semen sample obtained through masturbation directly from home or provide it in the laboratory's sample collection room. If the semen sample is brought from home, it should ideally be delivered to the laboratory within an hour of collection and kept at temperatures above 20ºC. In the laboratory, the semen is processed to separate and concentrate the best sperm in a culture medium, enhancing their fertilization capability.
After follicular aspiration, there may be mild abdominal discomfort, which can be alleviated with analgesics and tends to diminish throughout the day. Resting is recommended on that day. Some women may experience slight vaginal bleeding. However, if fever, severe pain, or excessive bleeding occurs, informing the doctor immediately is crucial. These symptoms are infrequent.
Starting from the day of follicular aspiration, the woman receives daily hormonal support with progesterone. The most common administration routes are vaginal, oral, intramuscular, or subcutaneous. Intramuscular administration is widespread in the United States.
This hormonal supplementation should be continued for several days until pregnancy is confirmed through a Beta hCG blood test. If pregnancy occurs, the supplementation should be continued until 7-8 weeks of amenorrhea. Some evidence suggests that supplementary progesterone use enhances embryonic implantation and supports the maintenance of pregnancy. If pregnancy does not occur, hormonal supplementation is stopped to allow menstruation.
c. Fertilization and embryonic development
Fertilization commences when sperm cells encounter the protective covering of the oocyte known as the zona pellucida. The process concludes with the dissolution of the pronuclei in a stage called syngamy.
During in vitro fertilization (IVF), oocytes are placed in small glass capsules immediately after they have been retrieved from the follicle. These capsules contain a culture medium, surrounding cells, and sperm cells and are kept in an incubator to facilitate fertilization. It can be challenging to determine the maturity of oocytes since they are fully covered by granulosa cells. As a result, the fertilization rates with conventional IVF are lower compared to a technique called intracytoplasmic sperm injection (ICSI), where mature oocytes are easily identified after stripping them from the surrounding cells using an enzyme called hyaluronidase. In ICSI, only mature oocytes are injected with a sperm cell, and this has become the preferred method in most cases.
Fertilization is confirmed by examining the pronuclei, which are the male and female nuclei, under a microscope 16 to 20 hours after co-incubating the gametes. In about 4% of cases, fertilization may not occur, resulting in no oocytes being fertilized or embryos failing to develop. In such instances, the doctor will not transfer any embryos, discontinue the treatment, and analyze the possible causes. To minimize this possibility, many fertility centers now opt for ICSI directly unless the couple has a proven fertility history with previous children.
The fertilization rate in IVF is approximately 70% when the gametes are normal. However, this rate can vary depending on the morphological characteristics of the gametes, the woman's age, the cause of infertility, and various environmental factors. These environmental factors include the quality and sterility of the culture media, air purity within the laboratory and incubators, temperature fluctuations, and pH levels.
In cases of male infertility where sperm cells cannot fertilize naturally, intracytoplasmic sperm injection (ICSI) is advised. This technique involves fertilizing each oocyte with a single sperm cell obtained from either semen or surgically retrieved from the epididymis, a duct located at the outflow of the testicle that transports sperm cells outward or even directly from the testicle itself.
d. Embryo transfer
The embryo transfer procedure is performed outpatient in a surgical unit, typically without requiring analgesia or anesthesia. It takes around 15 minutes to place the embryos into the uterine cavity delicately. A thin, smooth, and inert plastic tube, known as a catheter, is gently inserted through the uterine cervix to deposit the embryos in the uterine cavity. To facilitate the accurate placement of the embryos, the patient must arrive with a full bladder as the catheter's tip is visible during an abdominal ultrasound, allowing for precise positioning.
Embryo implantation usually occurs on the fifth day after fertilization. Depending on the specific circumstances, embryos can be transferred between the second and fifth day of their development. If the transfer occurs on the second or third day, the embryos develop in the uterine fluid until they reach the endometrium for implantation. In exceptional cases, when necessary, the transfer can be performed into the fallopian tubes through mini-laparoscopy, requiring fasting due to general anesthesia. In such cases, the transfer occurs on the second or third development day.
Following the embryo transfer, the patient rests for half an hour at the clinic. While observing partial rest for one to two days is recommended, it does not appear to be essential for successful outcomes. Some centers have reported positive pregnancy results without emphasizing strict rest.
Around 21 to 23 days after the embryo transfer, a transvaginal ultrasound can be conducted to visualize the gestational sac inside the uterus. It is usual for some women to experience slight vaginal bleeding following the transfer, which is typically not a cause for concern. Nine days after the transfer, approximately 13 days after follicular suction, the HCG hormone can be measured in the woman's blood to determine pregnancy. The HCG hormone's levels double every 1 to 2 days, enabling consecutive measurements to provide valuable insights into the quality of the gestation before confirming through ultrasound.
2. INTRACYTOPLASMIC SPERM INJECTION (ICSI) IN THE OOCYTE
ICSI, which stands for Intracytoplasmic Sperm Injection, is a specific technique within the broader process of in vitro fertilization (IVF). The procedure remains the same as described earlier, with one notable exception: the fertilization stage.
In traditional IVF, oocytes are co-incubated with laboratory-prepared sperm cells, which are collected using a column to select the best and most mobile cells. However, in ICSI, the sperm cells undergo the same preparation process but are individually chosen using a fine glass tube. These selected sperm cells are injected directly into mature oocytes' cytoplasm, previously separated from the cumulus cells (a protective covering formed by the granulosa cells surrounding the oocyte) to ensure their maturity. Only mature oocytes are subjected to the injection. The fertilization rate is evaluated after 24 hours.
ICSI significantly reduces total fertilization failure, often caused by undetected oocyte immaturity. Initially, this technique was primarily employed in cases of severe male factor infertility, where there were concerns about the sperm cells' ability to penetrate the oocyte membranes. Over time, it has also been adopted for unexplained infertility cases. Currently, ICSI is the most widely utilized method in various reproductive centers due to its favorable outcomes and the detailed assessment it allows for both oocyte maturity and sperm injection.
EFFICIENCY OF IVF/ICSI PROCEDURES
The effectiveness of assisted reproductive procedures can be evaluated by considering various measures. While the pregnancy rate following follicular aspiration or embryo transfer is commonly used, it is crucial to account for the spontaneous miscarriage rate, which is approximately 15%. Therefore, the most accurate efficiency measure is the birth rate or live births per 100 follicular aspiration cycles or embryo transfer cycles.
The efficiency of these procedures is influenced by the expertise of the medical professionals and the quality of the fertility center's equipment. However, certain factors can impact the chances of pregnancy regardless of the center's quality. These factors include the woman's age and the quality of the transferred embryos. The ability to freeze good-quality embryos for future use is also an important consideration.
Tables 1 and 2 below present pregnancy rates per embryo transfer based on the number of embryos transferred and the age of the women, respectively. These results are derived from data from Chile and Latin America and reported in the "Latin American Registry of Assisted Reproduction (RLA)". Furthermore, it is shown that optimal embryo chromosomal analysis (PGD) enhances the results (see p.44).
Table 1: Clinical pregnancy rate according to the number of transferred embryos in Assisted Reproduction procedures (IVF+ICSI)
Clinical pregnancy rate according to woman's age in Assisted Reproduction procedures (IVF+ICSI)
MULTIPLE PREGNANCIES BY ASSISTED REPRODUCTIVE PROCEDURES (IVF + ICSI)
The occurrence of multiple pregnancies in Assisted Reproductive Procedures (IVF + ICSI) is influenced by the number of embryos transferred and the woman's age. The global rate of multiple gestations is approximately 23%, indicating that out of 100 pregnancies, 23 involve two or more gestational sacs. Notably, 10% of these multiple pregnancies naturally result in the loss of one sac, usually before the 12th week of pregnancy. The outcome of twin pregnancies, considering appropriate medical care and the mother's physical condition, is comparable to that of single pregnancies. However, triple and quadruple pregnancies carry a higher risk of miscarriage, intrauterine fetal death, premature birth, and neonatal complications. These factors can result in severe consequences for newborns from triplet gestations or higher. To mitigate the risk of multiple gestations, reducing the number of transferred embryos is necessary, which, in turn, impacts the overall success rate of achieving pregnancy. This aspect should be extensively discussed between the medical team and the couple. Typically, in women under 38 years old, the transfer of 1 to 2 embryos is recommended. In contrast, in older women, the decision depends on various factors such as the number and quality of embryos, the cause of infertility, embryonic development stage, age, and previous treatment history. Table 3 provides information on multiple gestation rates based on the number of transferred embryos.
Rate of Multiple Gestation according to the number of transferred embryos in Assisted Reproduction procedures (IVF+ICSI)
LIKELY COMPLICATIONS OF THE ASSISTED REPRODUCTIVE TECHNIQUES (TARs)
1. Ovarian Hyperstimulation Syndrome: It is an ovary's hyper response to ovulation stimulation, resulting in excessive developing follicles. Enlarged ovaries, elevated plasma estradiol levels, abdominal distention, nausea, and respiratory distress characterize this condition. In severe cases, vascular dysfunction, reduced urine production, coagulation disturbances, and impaired kidney function may occur, leading to fluid accumulation in various body parts.
Ovarian Hyperstimulation Syndrome (OHSS) is a temporary condition that may necessitate hospitalization for management and monitoring. The administration of HCG injection typically triggers it. Severe symptoms are observed in 1% to 3% of stimulated cycles, with a higher likelihood in young women with polycystic ovary syndrome.
In some instances, drainage of accumulated fluid in the abdominal cavity may be necessary to alleviate distention. With current knowledge and timely monitoring of female hormone levels (Estradiol) and ultrasound assessments, the onset of this condition can be predicted. If severe symptoms are suspected, the stimulation cycle should be halted, and the HCG injection discontinued. Alternatively, oocyte aspiration, fertilization, and cryopreservation can be performed without embryo transfer in the current cycle, as pregnancy could exacerbate or prolong the progression of Ovarian Hyperstimulation Syndrome. In such cases, the embryo transfer is deferred to a later cycle.
The administration of intravenous albumin solution, initiated during follicular aspiration and continued for the first eight days, can help prevent mild to moderate hyperstimulation.
2. Tubal Pregnancy It refers to the spontaneous implantation of an embryo in the fallopian tube. The diagnosis can be made 21 days after embryo transfer using ultrasound, where a gestational sac in the tube can be observed. Suspicion arises when an intrauterine gestational sac is absent, and a subU Beta value of HCG is higher than 1500 mUI/ml. This complication occurs in 1% to 2% of cases, but in IVF cycles, the incidence increases to 4% due to the underlying uterine and tubal pathologies often present in these patients.
When diagnosed accurately, immediate intervention is required, typically through laparoscopic surgery or a chemotherapeutic drug known as Methotrexate. Methotrexate works by inhibiting the cellular multiplication of the embryos, reducing the risk of tubal rupture and intra-abdominal hemorrhage, which are the most significant dangers associated with tubal pregnancy.
3. Ovarian Torsion: Due to its increased size, the hyper-stimulated ovary can be prone to torsion, which involves the twisting of the ovary. This can lead to a compromised vascular supply and severe colic pains. Left unresolved, it can lead to necrosis (cell death), destruction, and hemorrhage within the ovary. Ovarian torsion occurs in less than 1% of cases and is considered a medical emergency. Surgical intervention is required, either through laparoscopic untwisting of the ovary to restore its blood flow and vitality or, in severe cases, the affected ovary is removed.
4. Birth Defects: The incidence of congenital disabilities in newborns conceived through in vitro fertilization (IVF) techniques is not higher than that of the general population. Studies conducted globally, including in Latin America, have shown that the rates of malformations in IVF-conceived babies do not exceed those found in the general population of reproductive age. The percentage of examined newborns with malformations typically falls within the range of 2% to 2.4%.
5. Other Complications: Although uncommon, some local complications are associated with transvaginal puncture during follicular suction in assisted reproduction procedures. These complications include hemorrhage from vaginal wall injury, pelvic infection leading to tub-ovarian abscess, ovarian bleeding, and injuries to adjacent structures such as the intestine. The occurrence of these complications is typically less than 1% of cases.
Implantation Failure.
It refers to the absence of pregnancy (detecting chorionic gonadotropin hormone in the blood) in a woman who has undergone embryo transfer. This diagnosis is specifically associated with "In Vitro Fertilization" treatments.
No unanimous agreement exists on the exact number of embryos or transfer cycles required to classify it as implantation failure. However, some consensus is that at least four embryos should be transferred in 3 to 4 cycles. It's important to note that certain factors should be considered, such as the development of the transferred embryo, the woman's age, the genetic normality of the embryo, and whether the embryo is fresh or cryopreserved.
The causes of implantation failure are diverse and can be categorized as follows:
a) Causes related to the embryo:
Today's primary known cause for an embryo failing to implant is an alteration in its chromosomal arrangement. Only a few embryos with this alteration can implant and continue their development. The majority either fail to implant altogether or implant, resulting in an early miscarriage. However, other genetic or functional abnormalities go beyond the number of chromosomes.
b) Causes related to the woman:
1) Endocrine-metabolic characteristics of the woman:
Evidence demonstrates that proper thyroid gland function and adequate control of blood glucose and body weight are crucial for ensuring successful embryo implantation.
2) Autoimmune diseases:
Conditions such as Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Scleroderma, among others, impact the normality of the embryo implantation process. It's worth noting that even in the absence of clinical disease, there may be markers of autoimmunity that could affect implantation. That's why investigating Antinuclear Antibodies and Anti-thyroid Antibodies is part of the examination in these patients.Antinucleares y Anti tiroides es parte del estudio en estas pacientes.
3) Genetic or acquired thrombophilias:
The presence of a history of thrombophilia is a relevant factor to consider. Although there is no consensus on whether it should be routinely examined in all patients, the familial or personal history of thrombosis or thrombophilia should be considered during the clinical evaluation..
4) Anatomical causes:
Any alteration or deformity, whether congenital or acquired, in the uterine cavity could potentially influence implantation..
c) Causes related to the man:
Sperm function plays a fundamental role in embryo formation. Traditional sperm indicators (semen analysis) have not been definitively linked to implantation failure but rather to infertility resulting from fertilization issues. On the other hand, sperm DNA fragmentation (nucleic acids in the sperm's nucleus located in its head) has been associated with recurrent miscarriage and implantation failure. This is an area of emerging knowledge.
d) Causes related to the uterine environment:
This area has seen significant progress in recent years. It refers to the ideal conditions for the uterus and endometrium to receive and sustain pregnancy until full term. Evaluations are conducted when the embryo reaches the uterus to determine its state.
Since the embryo possesses a genetic makeup distinct from the mother (combining genetics from both parents), the uterine environment must be prepared to recognize the embryo and accommodate it from an immunological standpoint (tolerance). To assess the uterine environment, the time the embryo normally reaches the endometrium for implantation, typically between the 5th and 8th day after ovulation (implantation window), is selected.
The currently assessable functions of the uterine environment that are crucial for successful implantation include:
a) Uterine and endometrial irrigation:
Using transvaginal ultrasound and Doppler of the uterine arteries and endometrium.
b) The endometrium:
By taking a sample of endometrial tissue with a small cannula, we can assess the following functions:
1) Endometrial maturation: Progesterone is the hormone that helps mature the endometrium, allowing for embryo adhesion and its invasion of the superficial epithelium, which enables implantation.
2) Immunological balance of the endometrium: Once the embryo is implanted, it continues to grow and develop, initiating the formation of the placenta. During this process, the recognition and tolerance of the embryo, as well as the formation of the placenta, heavily rely on two types of lymphocytes known as NK and T regulatory cells. They play a crucial role in ensuring successful implantation. Additionally, the presence of another type of lymphocytes called plasma cells indicates the existence of a hostile endometrium with chronic inflammation, which aggressively reacts and hinders embryo implantation.
3) State of the endometrial Biota: All our organs have a delicate balance of beneficial bacteria vital for proper functioning. These bacteria collaborate with the immune system in the endometrium to support implantation. When an inadequate Biota is present due to different bacteria than the usual lactobacilli, it can create an unfavorable environment for implantation.
This assessment of uterine irrigation and the endometrium allows us to identify potential explanations for implantation failures and devise various interventions (such as progesterone supplementation, immunomodulation, and administration of probiotics) to restore normality and enhance reproductive success.
3. BLASTOCYST OR EMBRYO VITRIFICATION
Blastocyst or embryo vitrification is a technique used for the cryopreservation of embryos. This process involves the rapid freezing of embryos after applying cryoprotectants to prevent crystal formation and potential cell damage. The vitrified embryos are then stored at ultra-low temperatures (-196 ºC) in labeled containers within liquid nitrogen tanks until thawed. Typically, blastocyst-stage embryos, which have reached day 5 of development, are selected for vitrification to maximize the chances of successful outcomes. Notably, not all fertilized oocytes can reach the blastocyst stage, with natural selection allowing only around 40% to 50% of fertilized oocytes to progress to this stage of development.
4. OOCYTES VITRIFICATION
Vitrification is a cold preservation process that can be performed using various methods. Mature oocytes not utilized immediately can be vitrified and stored for future use. If a woman decides not to use them, she can donate the vitrified oocytes or discard them, as they are considered cells. To utilize vitrified oocytes, they must undergo a thawing process and be inseminated through intracytoplasmic sperm injection (ICSI). Vitrification involves the rapid cooling of oocytes, which tightens the external membrane or zona pellucida, preventing spontaneous penetration by sperm cells. Once fertilized, the embryo undergoes development and is subsequently transferred to the patient's prepared uterine cavity through hormone administration. Alternatively, the embryo can be re-vitrified without compromising its biological potential.
ADDITIONAL REASONS FOR OOCYTE VITRIFICATION
1. Preservation of Fertility: Young women undergoing cancer therapy, which may harm their ovarian reserve, can opt for oocyte vitrification to preserve their fertility. As previously described, ovarian stimulation, like in vitro fertilization, retrieves the oocytes. The harvested oocytes are then assessed for maturity using hyaluronidase. Only mature (MII) oocytes are vitrified and stored in labeled special devices submerged in liquid nitrogen.
