Unexpected IVF Results

Jennifer M

January 10, 2023

Question

Hi Dr. Sher-

I just completed my first failed IVF cycle and I’m left shocked and confused by the results, for both egg retrieval and transfer. I am 38 years old, AMH is 5.12, FSH 6.3, follicle count around 40- No PCOS that we can see- normal appearing ovaries and pretty regular cycles. We went for IVF due to male factor- low sperm count around 5 mil per ml.

For my egg retrieval: 20 eggs were retrieved, but only 11 were mature. Of those 11, 5 were degenerated. I am still not quite sure what that means and have asked another medical professional about it who was unfamiliar. Only 6 could be fertilized with ICSI. Of those 6, 5 fertilized and 3 made it to blast. Of the 3 blast, 1 tested PGA normal.

I transferred my PGA normal last month and got pregnant. However the pregnancy stopped progressing at 6 weeks. I am now waiting to miscarry. It was a 5AA hatching blasts as well. I was told that the chance of miscarriage was only 10%.

I am looking to try again, but confused about the next steps. My RE doesn’t think anything should be done differently. However, I was very disappointed by egg retrieval and only having 6 eggs to work with considering my high follicle count. I have looked into degenerated eggs and found one article that points the finger to the egg retrieval process itself causing it by the drugs or the egg extraction itself. The article did not find a correlation with age as my doctor told me.

What is your experience with degenerated eggs? Can this be caused by uneven growth or over mature eggs? During my egg retrieval process, it seemed to me that my eggs were growing in 3 different groups in terms of size. I was not put on birth control prior.

Any advice on why my transfer failed? I have a history of polyps, but had one removed 2 months prior to doing the transfer. I had a fear of one growing during the transfer cycle with the estrace and my doctor thought he may have seen a small polyp, but I choose to transfer anyway. It seems I have had polyps in cycles where medication is given that affects estrogens levels and not in off cycles. For example, I had two develop, each in separate IUI cycles using letrozole. I did not develop any in my cycle without medication.

Sorry for all of the information. I don’t know where to turn now and don’t want my second IVF to be a repeat of the first.

Thank you for any advice you can offer!

Jennifer

Answer

One of the commonest questions asked by patients undergoing IVF relates to the likelihood of their eggs fertilizing and the likely “quality of their eggs and embryos. This is also one of the most difficult questions to answer. On the one hand many factors that profoundly influence egg quality; such as the genetic recruitment of eggs for use in an upcoming cycle, the woman’s age and her ovarian reserve, are our outside of our control. On the other hand the protocol for controlled ovarian stimulation (COS) can also profoundly influence egg/embryo development and this is indeed chosen by the treating physician.

First; it should be understood that the most important determinant of fertilization potential, embryo development and blastocyst generation, is the numerical chromosomal integrity of the egg (While sperm quality does play a role, in the absence of moderate to severe sperm dysfunction this is (moderate or severe male factor infertility a relatively small one). Human eggs have the highest rate of numerical chromosomal irregularities (aneuploidy) of all mammals. In fact only about half the eggs of women in their twenties or early thirties, have the required number of chromosomes (euploid), without which upon fertilization they cannot propagate a normal pregnancy. As the woman advances into and beyond her mid-thirties, the percentage of eggs euploid eggs declines progressively such that by the age of 40 years, only about one out of seven or eight are likely to be chromosomally normal and by the time she reaches her mid-forties less than one in ten of her eggs will be euploid.

Second; embryos that fail to develop into blastocysts are almost always aneuploid and not worthy of being transferred to the uterus because they will either not implant, will miscarry or could even result in a chromosomally abnormal baby (e.g. Down syndrome). However, it is incorrect to assume that all embryos reaching the blastocyst stage will be euploid (“competent”). ). It is true that since many aneuploid embryos are lost during development and that those failing to survive to the blastocyst stage are far more likely to be competent than are earlier (cleaved) embryos. What is also true is that the older the woman who produces the eggs, the less likely it is that a given blastocyst will be “competent”. As an example, a morphologically pristine blastocyst derived from the egg of a 30-year-old woman would have about a 50:50 chance of being euploid and a 30% chance of propagating a healthy, normal baby, while a microscopically comparable blastocyst-derived through fertilization of the eggs from a 40-year-old, would be about half as likely to be euploid and/or propagate a healthy baby.

While the effect of species on the potential of eggs to be euploid at ovulation is genetically preordained and nothing we do can alter this equation, there is, unfortunately, a lot we can (often unwittingly) do to worsen the situation by selecting a suboptimal protocol of controlled ovarian stimulation (COS). This, by creating an adverse intraovarian hormonal environment will often disrupt normal egg development and lead to a higher incidence of egg aneuploidy than otherwise might have occurred. Older women, women with diminished ovarian reserve (DOR) and those with polycystic ovarian syndrome are especially vulnerable in this regard.

During the normal, ovulation cycle, ovarian hormonal changes are regulated to avoid irregularities in production and interaction that could adversely influence follicle development and egg quality. As an example, small amounts of androgens (male hormones such as testosterone), that are produced by the ovarian stroma (tissue surrounding ovarian follicles) during the pre-ovulatory phase of the cycle enhance late follicle development, estrogen production by the granulosa cells (that line the inner walls of follicles), and egg maturation. However, over-production of testosterone can adversely influence the same processes. It follows that COS protocols should be individualized and geared toward optimizing follicle growth and development time while avoiding excessive ovarian androgen (testosterone) production and that the hCG “trigger shot” should be carefully timed.

In summary, it is important to understand the influence species, age of the woman as well as the effect of the COS protocol can have on egg/embryo quality and thus on IVF outcome. The selection of an individualized protocol for ovarian stimulation is one of the most important decisions that the RE has to make and this becomes even more relevant when dealing with older women, those with diminished ovarian reserve (DOR) and women with PCOS. Such factors will in large part determine egg competency, fertilization potential, the rate of blastocyst generation and indeed IVF outcome.

I strongly recommend that you visit www.SherIVF.com. Then go to my Blog and access the “search bar”. Type in the titles of any/all of the articles listed below, one by one. “Click” and you will immediately be taken to those you select. Please also take the time to post any questions or comments with the full expectation that I will (as always) respond promptly.

The IVF Journey: The importance of “Planning the Trip” Before Taking the Ride”
Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
The Fundamental Requirements For Achieving Optimal IVF Success
Use of GnRH Antagonists (Ganirelix/Cetrotide/Orgalutron) in IVF-Ovarian Stimulation Protocols.
Anti Mullerian Hormone (AMH) Measurement to Assess Ovarian Reserve and Design the Optimal Protocol for Controlled Ovarian Stimulation (COS) in IVF.
The “Biological Clock” and how it should Influence the Selection and Design of Ovarian Stimulation Protocols for IVF.
A Rational Basis for selecting Controlled Ovarian Stimulation (COS) protocols in women with Diminished Ovarian Reserve (DOR)
Diagnosing and Treating Infertility due to Diminished Ovarian Reserve (DOR)
Ovarian Stimulation in Women Who have Diminished Ovarian Reserve (DOR): Introducing the Agonist/Antagonist Conversion protocol
Controlled Ovarian Stimulation (COS) in Older women and Women who have Diminished Ovarian Reserve (DOR): A Rational Basis for Selecting a Stimulation Protocol
Optimizing Response to Ovarian Stimulation in Women with Compromised Ovarian Response to Ovarian Stimulation: A Personal Approach.
Egg Maturation in IVF: How Egg “Immaturity”, “Post-maturity” and “Dysmaturity” Influence IVF Outcome:
Commonly Asked Question in IVF: “Why Did so Few of my Eggs Fertilize and, so Many Fail to Reach Blastocyst?”
Human Growth Hormone Administration in IVF: Does it Enhances Egg/Embryo Quality and Outcome?
The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
Staggered IVF
Staggered IVF with PGS- Selection of “Competent” Embryos Greatly Enhances the Utility & Efficiency of IVF.
Staggered IVF: An Excellent Option When. Advancing Age and Diminished Ovarian Reserve (DOR) Reduces IVF Success Rate
Embryo Banking/Stockpiling: Slows the “Biological Clock” and offers a Selective Alternative to IVF-Egg Donation
Preimplantation Genetic Testing (PGS) in IVF: It should be Used Selectively and NOT be Routine.
IVF: Selecting the Best Quality Embryos to Transfer
Preimplantation Genetic Sampling (PGS) Using: Next Generation Gene Sequencing (NGS): Method of Choice.
PGS in IVF: Are Some Chromosomally abnormal Embryos Capable of Resulting in Normal Babies and Being Wrongly Discarded?
PGS and Assessment of Egg/Embryo “competency”: How Method, Timing and Methodology Could Affect Reliability
IVF outcome: How Does Advancing Age and Diminished Ovarian Reserve (DOR) Affect Egg/Embryo “Competency” and How Should the Problem be addressed.

______________________________________________________

ADDENDUM: PLEASE READ!!

INTRODUCING SHER FERTILITY SOLUTIONS (SFS)

Founded in April 2019, Sher Fertility Solutions (SFS) offers online (Skype/FaceTime) consultations to patients from > 40 different countries. All consultations are followed by a detailed written report presenting my personal recommendations for treatment of what often constitute complex Reproductive Issues.

If you wish to schedule an online consultation with me, please contact my assistant (Patti Converse) by phone (800-780-7437/702-533-2691), email (concierge@SherIVF.com) or, enroll online on then home-page of my website (www.SherIVF.com).

PLEASE SPREAD THE WORD ABOUT SFS!

Geoff Sher

_______________________________________________________________

ADDITIONAL INFORMATION:

I am attaching online links to two E-books which I 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