• Human embryo development is a marvel of intricate processes, including reprogramming, sequential cleavage divisions, mitotic chromosome segregation, and embryonic genome activation. However, the journey towards a successful pregnancy is not without its challenges, as chromosomal abnormalities can occur during germ cell and preimplantation embryo development, leading to early implantation failures and pregnancy losses.

  Two decades ago, a groundbreaking technique emerged: full embryo karyotyping through preimplantation genetic sampling (PGS)/preimplantation genetic testing for aneuploidy (PGT-A). This method revolutionized the field by allowing us to identify and characterize an embryo’s karyotype, enabling the selective transfer of euploid embryos (those with a complete set of 46 chromosome! into the uterus. This innovation led to a remarkable increase in implantation and birth rates, coupled with a significant reduction in early pregnancy losses following in vitro fertilization (IVF). Today, PGS/PGT-A is a standard practice worldwide.

  However, this advancement presents a moral and ethical dilemma. Many IVF programs require patients to consent to the disposal of all aneuploid embryos—those with irregular chromosome quotas. Recent evidence has raised questions about whether some aneuploid embryos, when transferred, can “autocorrect” during development, potentially resulting in healthy babies. This dilemma forces us to reconsider our approach to discarding embryos.

  The crux of this embryo “autocorrection” lies in the fact that many embryos labeled as aneuploid through PGS/PGT-A also contain chromosomally normal (euploid) cells. This coexistence of aneuploid and euploid cells within the same embryo is known as “mosaicism.”

  In response to this complexity, more IVF practitioners are opting to cryobank certain PGS/PGT-A-identified aneuploid embryos, preserving the option for future transfer. To make informed decisions in such cases, it’s crucial to understand the two types of embryo aneuploidy:

  Meiotic aneuploidy: This results from chromosomal numerical abnormalities originating in the egg or sperm during preconceptual maturational division (meiosis). Meiotic aneuploidy is permanent, affecting all subsequent embryo cells and often leading to implantation failure, early pregnancy loss, or chromosomal birth defects.
  2.    Mitotic aneuploidy (Mosaicism): This occurs when some cells of a meiotically normal early embryo, in the process of cell replication (mitosis), mutate and become aneuploid after fertilization. The outcome depends on whether aneuploid or euploid cells predominate. Mosaic embryos with more euploid cells are likely to undergo autocorrection once arriving in the uterus, leading to the propagation of chromosomally normal and healthy pregnancies.

  Differentiating between these two types of aneuploidy is crucial, and next-generation gene sequencing (NGS) has significantly improved the accuracy of full embryo karyotyping, aiding in the diagnosis of mosaicism.

  Several factors influence the autocorrection potential of mosaic embryos, including the stage of embryo development at diagnosis, affected chromosomes, the complexity of aneuploidy, and the percentage of aneuploid cells. Embryos diagnosed as “mosaic” at earlier stages may autocorrect as they develop into blastocysts. Segmental mosaic aneuploidies and lower percentages of mitotically aneuploid cells in the blastocyst increase the chances of autocorrection.

  Transferring embryos with autosomal meiotic trisomy often results in implantation failure, miscarriage, or the birth of a defective child. In contrast, autosomal mitotic trisomies, which can autocorrect, require careful consideration. Patients are advised to undergo prenatal genetic testing and be prepared to make difficult decisions if necessary.

  When dealing with meiotic autosomal monosomy, the chances of a viable pregnancy are minimal, with those that do implant often ending in early spontaneous miscarriage. However, mosaic autosomal monosomic embryos can often autocorrect, making them a viable option for transfer. Nevertheless, full disclosure to patients and a commitment to prenatal genetic testing are essential in such cases.

  When we biopsy an embryo for PGS/PGT-A, we test only a few cells, typically around six. If at least one of these cells is healthy (euploid) while the others are not (aneuploid), it’s called a “mosaic” embryo, and is potentially capable of self-correcting in the womb and leading to a healthy baby. On the other hand, if all the tested cells are aneuploid, it’s highly likely that the rest of the untested cells in the embryo are also abnormal, making it an unsalvageable, meiotically aneuploid embryo. However, we can’t be certain because we haven’t tested all the cells. So, even if we diagnose an embryo as aneuploid, in a few cases, it might still be mosaic and have a chance to develop normally in the uterus.

  In summary, while we can confidently diagnose euploid embryos, diagnosing mosaic embryos is currently not perfect, and there’s a possibility that some may have the potential to develop into healthy babies. Embryo mosaicism adds complexity to the world of IVF, forcing us to navigate a delicate balance between minimizing risks and providing opportunities for patients to have healthy babies. The evolution of diagnostic techniques like NGS has brought us closer to understanding and harnessing the potential of mosaic embryos, but the journey remains intricate and ethically charged.

  PLEASE SHARE THIS WITH OTHERS AND HELP SPREAD THE WORD!!

   

  Herewith are  online links to 2  E-books recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

  1. From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) ; https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

   

  1. Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link ;https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

   

  I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

  If you are interested in having an online consultation with me, please contact my assistant, Patti Converse at 702-533-2691 or email her at concierge@sherivf.com\

   

Please re-post in English!

Geoff Sher

“Empty Follicle Syndrome” is a misleading term because follicles always contain eggs. However, some eggs may have difficulties detaching and being retrieved. This is more likely to happen when multiple attempts are needed to retrieve an egg from a follicle, indicating the egg may have chromosomal abnormalities.

The hormonal environment created during controlled ovarian stimulation plays a significant role in egg development. In certain cases, follicles may not release their eggs during retrieval, leading to the misconception of “empty” follicles.

This situation is most commonly encountered in older women, those with diminished ovarian reserve (DOR), and women with polycystic ovarian syndrome (PCOS). To address this problem, personalized protocols for controlled ovarian stimulation and careful administration of the hCG trigger shot are important.

The hCG trigger shot is given after optimal ovarian stimulation to initiate the process of reducing the number of chromosomes in the egg. It also helps the egg detach from the follicle’s inner wall. This allows for easier retrieval during the egg retrieval procedure.

Women with increased LH activity, such as older women, those with DOR, and women with PCOS, are more susceptible to the negative effects of LH-induced ovarian testosterone. Excessive LH activity can compromise egg development and increase the chances of chromosomal abnormalities. Medications like clomiphene and Letrozole can stimulate LH release, and certain drugs containing LH or hCG can have negative consequences.

Individualizing the controlled ovarian stimulation protocol, determining the correct dosage and type of hCG trigger, and administering it at the right time are crucial. The recommended dosage of urinary-derived hCG products is 10,000 units, while for recombinant DNA-derived hCG, the optimal dosage is 500 micrograms. A lower dosage of hCG can increase the risk of chromosomal abnormalities in the eggs and negatively impact the outcome of IVF.

Understanding the role of LH activity, the effects of medications on hormone release, and the importance of personalized protocols are vital. By optimizing these factors, the risk of failed egg retrieval and “empty follicle syndrome” can be minimized, improving the chances of successful IVF outcomes.

PLEASE SHARE THIS WITH OTHERS AND HELP SPREAD THE WORD!!

Herewith are  online links to 2  E-books recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1. From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) ; https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link ;https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

If you are interested in having an online consultation with me, please contact my assistant, Patti Converse at 702-533-2691 or email her at concierge@sherivf.com\

Please re-post in English!

Geoff Sher

Please re-post in English!

Geoff Sher

• UNEXPLAINED” INFERTILITY: A RATIONAL APPROACH TO MANAGEMENT

Infertility affects y 10%-15% of couples who are unable to conceive. In some cases, the cause of infertility cannot be determined using conventional diagnostic methods, leading to a diagnosis of “unexplained infertility.” However, it is important to note that in most cases labeled as “unexplained infertility,” a more thorough evaluation could have revealed an underlying cause. There are two main groups of individuals diagnosed with unexplained infertility: those without any biological problems hindering pregnancy, and those with unidentified reasons due to limited medical information or technology. Fortunately, advancements in testing techniques have made it easier to diagnose and treat infertility in the latter group.

To make a presumptive diagnosis of unexplained infertility, healthcare providers need affirmative answers to several questions. These include whether the woman is ovulating normally, whether the couple engages in regular intercourse during the periovulatory phase of the menstrual cycle, whether the fallopian tubes are normal and open, whether endometriosis can be ruled out, whether the male partner has normal semen parameters (especially sperm count and motility), and whether the presence of high concentrations of antisperm antibodies in the man or woman’s blood is associated with sperm incapacitation.

The diagnosis of unexplained infertility depends on the thoroughness of the healthcare provider in attempting to rule out all potential causes. The fewer tests conducted, the more likely it is that  a presumptive diagnosis of “unexplained” infertility will be made. Below are a few causes of infertility that are often missed leading to the cause of infertility being mischaracterized as being “unexplained: :

• Subtle abnormalities involving the fallopian tubes without causing them to be “blocked”, often go unnoticed. Examples include subtle peritubal adhesions and/ or developmental or acquired defects involving the tubal fimbria (i.e., the finger-like “petals” at their outer ends), can prevent the collection and transportation of eggs to meet sperm. Detecting these conditions requires direct visualization of lesions through laparoscopy or laparotomy
• Chromosomal abnormalities in eggs or embryos can also contribute to infertility. Both eggs and embryos must contain the correct number of chromosomes (euploid) for successful fertilization and implantation. Until recently, there was no reliable method to determine their chromosomal status. However, the introduction of preimplantation genetic screening/testing (PGS/T), using genetic tests like next generation gene sequencing (NGS) has enabled the identification of embryo, numerical chromosomal abnormalities (aneuploidy) which when present will prejudice fertility. PGS/T has become an essential tool in diagnosing infertility.
• Luteinized Unruptured Follicle (LUF) Syndrome is another condition that can contribute to unexplained infertility. In this condition, eggs become trapped in the follicle and are not released, despite routine tests indicating normal ovulation. Hormonal dysfunction related to ovulation can also negatively impact the preparation of the uterine lining, hindering normal implantation.
• Immunologic implantation dysfunction (IID) can occur when the woman’s or man’s immune system attacks sperm cells, rendering them immobile or causing their destruction. Additionally, immunologic dysfunction involving the uterine lining can lead to early rejection of the implanting embryo, often before the woman realizes she has conceived.
• Cervical infection, specifically Ureaplasma Urealyticum infection of the cervical glands, can prevent sperm from reaching the eggs in the fallopian tubes. This type of infection is usually undetectable through routine examination or cervical culturing methods.
• Mild or moderate endometriosis is a condition associated with the production of “pelvic toxins” that reduce the fertilization potential of eggs. Approximately one-third of women with endometriosis also experience IID. Detecting mild or moderately severe endometriosis requires direct visualization of lesions through laparoscopy or laparotomy, and identifying IID requires sophisticated tests performed by specialized Reproductive Immunology Reference Laboratories. In some cases of early endometriosis the lesions are “nonpigmented” and  cannot even be detected through direct vision, yet they can significantly impact fertility through establishing a “toxic” intrapelvic environment that compromises competency of the egg as it traverses the pelvic environment during passage from the ovary to the tube.
• Psychological factors can also influence fertility. Stress and negativity can interfere with hormonal balance and decrease the ability to conceive.
• Mild Male Factor infertility that are not readily detected through routine semen analysis.
• Antisperm antibodies (ASA) in the man or in the woman. This can only be diagnosed using high specialized blood and sperm test.

Management:

When it comes to managing “Unexplained Infertility,” a personalized approach is crucial for success. The first step is to identify any underlying causes whenever possible. For those experiencing ovulation dysfunction due to hormonal imbalances, ovulation induction with oral or injectable fertility drugs is often recommended. In cases where an IID is detected, selective immunotherapy will be required and in cases cervical mucus hostility is caused by a ureaplasma infection, specific and simultaneous antibiotic therapy becomes necessary.

For younger women (under 39 years) facing issues with sperm migration through the cervix, uterus, and fallopian tubes, intrauterine insemination (IUI) with or without controlled ovulation stimulation (COS) is often the recommended course of action. However, if these treatments prove ineffective, or if the woman is over 39 years old, has IID, harbors significant concentrations of antisperm antibodies, or has structural tubal abnormalities, IVF becomes the preferred option. In cases of male infertility that are intractable, moderate, or severe, where natural fertilization seems unlikely, injecting sperm directly into the egg through a procedure called intracytoplasmic sperm injection (ICSI)/IVF  is necessary to achieve fertilization.

It is an undeniable truth that the majority of infertility cases can be diagnosed, which makes it disheartening when the label of “unexplained infertility” is used as an excuse for not conducting a thorough evaluation of the problem. Couples should not simply accept a diagnosis of “unexplained infertility” at face value. Instead, they should actively seek to have their treating physician identify the specific cause of their infertility, as treatment is most likely to be successful when the root cause is fully understood. By taking charge of their reproductive health and exploring all possible avenues, couples can increase their chances of achieving their dream of starting a family.

 _____________________________________________________

PLEASE SHARE THIS WITH OTHERS AND HELP SPREAD THE WORD!!

Herewith are  online links to 2  E-books recently  co-authored with  my partner at SFS-NY  (Drew Tortoriello MD)……. for your reading pleasure:

1. From In Vitro Fertilization to Family: A Journey with Sher Fertility Solutions (SFS) ; https://sherfertilitysolutions.com/sher-fertility-solutions-ebook.pdf

1. Recurrent Pregnancy Loss and Unexplained IVF Failure: The Immunologic Link ;https://drive.google.com/file/d/1iYKz-EkAjMqwMa1ZcufIloRdxnAfDH8L/view

I invite you to visit my very recently launched “Podcast”,  “HAVE A BABY” on RUMBLE;   https://rumble.com/c/c-3304480

If you are interested in having an online consultation with me, please contact my assistant, Patti Converse at 702-533-2691 or email her at concierge@sherivf.com\