Case Study: Poor Quality Eggs/Embryos in Young Women With Normal Ovarian Reserve: Case #1 – Polycystic Ovarian Syndrome

02 Nov
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After contemplating how to make my blog posts more helpful to patients with unexplained IVF failures, I have decided to profile the case histories of a number of patients who sought my input after having failed at IVF (often repeatedly). I will try to identify the various potentially remediable reasons for failure, and then make specific recommendations as to how I personally would address (or have addressed) these issues. In some cases, the patients underwent subsequent treatment with me, in which case I have indicated the details and outcome of their treatment.

To make this exercise useful, I have decided to discuss these cases in specific categories that will highlight often overlooked factors that can lead to (unnecessary) IVF failure.

Cases will be presented in three categories:

  1. Women who ended up with poor quality eggs/embryos.
    a. Younger women with normal or exaggerated ovarian reserve
    b. Older women (over age 39) with normal and/or diminished ovarian reserve (DOR)
  2. Women who failed to conceive because of embryo implantation dysfunction
  3. IVF failures following third party IVF (Egg Donation and Gestational Surrogacy)

Please note that the case reports and commentaries will include links to other articles on this site that will hopefully expand on the explanations given.

The first three posts in this series will address Category 1.a – younger women who ended up with poor quality eggs/embryos.

Today’s post profiles a patient with Polycystic Ovarian Syndrome (PCOS) and the various effects of this condition (along with the prescribed IVF protocols) on egg/embryo quality. Friday’s post will discuss a case in which poor egg/embryo quality was due to an occult male factor infertility issue. Next Tuesday I will post case #3, which will detail a patient with poor egg/embryo quality due to advanced endometriosis.

In coming weeks, I will address more cases under the current heading and will then go on to cases involving the other categories listed above.

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Case History #1

“Ann” aged 34 years had been trying to conceive for 3 years. She had never conceived previously (Primary Infertility) in spite of having a fertile male partner, undergoing four attempts at intrauterine insemination using clomiphene citrate (Serophene) for induction of ovulation, and 2 prior IVF procedures. Her menstrual periods were grossly irregular with cycles ranging from 20–35 days apart. Her day-3 blood hormone levels were as follows: Follicle Stimulating Hormone (FSH): 4.5 MIU/ml; Luteinizing Hormone (LH): 9.1 MIU/ml; Estradiol (E2): 62pg/ml; Antimullerian Hormone (AMH): 5.6

Ann had been diagnosed with Polycystic Ovarian Syndrome (PCOS). Both of her IVF treatment cycles (prior to consulting with me) involved ovarian stimulation with Menopur and Ganirelix (beginning on day 6 of stimulation). By the time of the hCG trigger (7-8 days after stimulation started) most of her 40+ follicles were still somewhat under-developed measuring 15-17mm in mean diameter, having not yet attained optimal size (18-22mm), and her peak blood [E2] exceeded 6,000 pg/ml. She was told that she needed to be triggered with hCG at that time to stop the process of follicle growth, which would prevent her blood [E2] from spiraling out of control and potentially causing her to develop the life-endangering condition of Severe Ovarian Hyperstimulation Syndrome (OHSS). In both of these prior cycles, only about 40% of the follicles yielded eggs at the time of egg retrieval. Many of her eggs were immature (MI’s), and those that were mature (MII’s), yielded poor quality embryos after fertilization by ICSI.

She had developed moderately severe ovarian hyperstimulation (abdominal fluid collection, backache and some difficulty in breathing) prior to the embryo transfer (ET), which in both cycles involved the transfer of three (3) day-3, poor quality embryos to her uterus. She did not conceive, but her ovarian hyperstimulation got worse in the ensuing days. She experienced a reduction in urine output, diarrhea, worsening abdominal pain, and progressively more difficult breathing. These symptoms and signs, along with abnormal blood tests pointed to OHSS, which is a life-threatening condition, which fortunately, in the absence of pregnancy is self-limiting and disappears 10-14 days after the hCG shot. Thus, since she did not conceive, she recovered about 10 days later.

Commentary
In my opinion, the reason for the poor egg/embryo quality in these two IVF cycles preceding her final attempt with us, was likely due to the IVF stimulation protocol that was used, as well as premature timing of the hCG trigger. In my experience, women with elevated basal blood [LH] do poorly on protocols that do not down-regulate the LH before and during the stimulation cycle (women with PCOS commonly have elevated blood [LH]). Since the “antagonist” (Ganirelix) was only commenced six days after the stimulation was initiated with Menopur, by the time it suppressed her high pituitary LH production, her eggs had already been exposed to excessive LH-induced ovarian male hormones or androgens (mainly testosterone). It was probably this that had a deleterious effect on her developing eggs and subsequently on her embryo quality.

In addition, because her eggs developed poorly, many of them remained firmly attached to the inner walls of her follicles and could not be retrieved. This would serve to explain why she had so many “empty follicles”. It also probably explains the low percentage of mature (MII) eggs produced in prior cycles and her subsequent poor quality embryos that ultimately led to failed IVF. In addition, Menopur (which aside from FSH also contains 50% LH/hCG) was not the ideal gonadotropin to use in this case, because the additional LH would simply add more “fuel to the fire”.

Another factor here is that the hCG trigger was administered relatively early in her cycle, such that her follicles did not have sufficient time to develop optimally before the process of development was abruptly arrested by the trigger. This was clearly done deliberately in an attempt to reduce the risk of OHSS developing…unsuccessfully in this case.

Follow up
The patient subsequently went through a cycle of COS with me. We prepared Ann for an IVF cycle by starting her on a birth control pill and thereupon, given that she was a “high responder,” we put her on a low-dosage, long pituitary down-regulation protocol with Follistim and Luveris to properly maintain a low LH. She produced 47 follicles which by day 8 of stimulation were (14m-16mm) and her [E2] was 2700pg/ml. At this point I commenced the “prolonged coasting” process by discontinuing the gonadotropins while maintaining the daily “agonist” (Lupron) injections. This would give her follicles and eggs an opportunity to develop optimally (18-22mm) before administering the hCG trigger. Her blood [E2] rose and peaked at 7700pg/ml by day 9 and then began to fall, reaching below 2,500pg threshold by day 12. At this point the follicles were mostly 18-22mm in mean diameter and I administered 10,000U of hCG (Profasi) to trigger ovulation. We retrieved 42 eggs, 34 of which were mature (MII’s) and were fertilized using ICSI. Thirty-one (31) MII’s fertilized and by day-3 post-ICSI, most were 6-9 cells. By day-6, we counted 11 expanded blastocysts and transferred two of these into her uterus. She conceived with a singleton and at this time is nearing the end of the 1st trimester and is doing well. This treatment approach likely prevented OHSS and helped optimize embryo quality.

Addendum:It is important to understand that IVF is an ART-Science blend and not all practitioners agree on the same strategies.Thus, in the final analysis, it is important, after discussion with your personal doctor, to follow his/her advice to the letter.Feel free to present your case history in the comments and I will do my best to offer my opinion.

179 Comments

  • Smithb0 says:

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  • Shela says:

    Hi Dr. Sher,

    I am 30 years old, (just had my birthday a few weeks ago and am still getting used to say I’m 30)!

    I am being treated as a PCO patient because of my 35 day cycles and my AMH of 7.64. I don’t seem to have any other PCO symptoms besides that I have a very difficult time losing weight despite eating healthy, low carb and active lifestyle. I am not severely over weight but should be thinner for how strict I am!

    One year ago I had a large (10 mm) endometrioma removed from my right ovary in a laparoscopic surgery. No other evidence of endometriosis was found.

    I have been trying to conceive for over a year and have tried several timed intercourse cycles with clomid and ovidrel, and 2 IUIs with clomid and ovidrel. (I ovulated each time but never got a positive result). I had an HSG done recently and my uterus is normal and tubes are clear. My partner’s sperm sample is excellent.

    I did my first IVF cycle in late November/early December. I was on Oral contraceptive pills for 2 months prior to stimulation, then used 150 iu follistim and 150 menopur for 8 days, adding in ganirelix on day 5 of stimulation. On day 8 I administered the HCG trigger (10,000) and appeared to have 22 follicles at least.

    At Egg Retrieval they got 16 eggs (11 were mature) and all 11 fertilized via ICSI. By day 5, 10 embryos were still progressing as morulas, but only one was at the early blastocyst stage and another was a morula that was transitioning into early blast stage. They transferred the early blastocyst on day 5 and told me on day 6 that none of the 9 embryos left were good enough to freeze. 9 days past 5 day transfer I got a positive HCG level of 7.4. It was a chemical pregnancy and didn’t last more than a few days.

    I am currently on OCP awaiting my next IVF cycle. My RE is having me do 5.5 weeks straight of OCP this time and in one week, (while on OCP) I will start andogren patches and estrace for 10 days. After the 10 days of androgen/estrogen I will administer lupron for 7 days. Immediately following the end of lupron I am to begin my stimulation meds. I will be doing follistim and menopur again, with added microdose HCG and ganirelix. I have also been taking metformin, coq10, myo-inositol, and vitamin d since the end of my last cycle about a month ago.

    I would greatly welcome your advice on my former protocol and what you think went wrong to yield sub quality embryos and my future protocol and if there are adjustments to the medications or protocol you’d suggest I might discuss with my RE to get a better outcome this time! Thank you so much!!

    • Geoffrey Sher says:

      Hi Shela,

      We absolutely should talk because I think I can be of help here.

      First, please understand that since you had an endometrioma, you do have advanced endometriosis and that 1/3 of women with this condition will also have an immunologic implantation dysfunction associated with activated uterine natural killer cells. If you have this issue, even IVF will likely not succeed unless it is addressed through selective immunotherapy with Intralipid/steroids/Lovenox (see below.

      Second, with PCOS, the protocol used for ovarian stimulation is critical and central to success. The reason is that there is an abnormal hormone environment in the ovaries of PCOS women. This needs to be carefully and strategically addressed by the protocol used. There is no place for a one size fits all approach here (see below).

      I strongly recommend that you visit my NEW personal website at http://www.DrGeoffreySherIVF.com and when you reach the home page, go to my new Blog find the “search bar” and 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.

      • Controlled Ovarian Stimulation (COS) for IVF: Selecting the ideal protocol
      • IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation(COS)
      • The BCP: Does Launching a Cycle of Controlled Ovarian Stimulation (COS). Coming off the BCP Compromise Response?
      • IVF Failure and Implantation Dysfunction: The Role of Endometrial Thickness, Uterine Pathology and Immunologic Factors
      • Unexplained IVF Failure
      • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 1-Background
      • Immunologic Implantation Dysfunction (IID) & Infertility (IID):PART 2- Making a Diagnosis
      • Immunologic Dysfunction (IID) & Infertility (IID):PART 3-Treatment
      • Thyroid autoantibodies and Immunologic Implantation Dysfunction (IID)
      • Immunologic Implantation Dysfunction: Importance of Meticulous Evaluation and Strategic Management:(Case Report)
      • Recurrent Pregnancy Loss (RPL): Why do I keep losing my Pregnancies?
      • Traveling for IVF from Out of State/Country–
      • A personalized, stepwise approach to IVF at SIRM”; Parts 1 & 2 (posted March, 2012)
      • The Role of Nutritional Supplements in Preparing for IVF
      • Frozen Embryo Transfer (FET): What Does it Involve?
      • Hereditary Clotting Defects (Thrombophilia)
      • Launching Ovarian Stimulation with a BCP: How Does it Affect Response?
      • Endometriosis and Infertily
      • Treating Ovarian Endometriomas with Sclerotherapy.
      • Preventing Severe Ovarian Hyperstimulation Syndrome (OHSS) with “Prolonged Coasting”
      • Understanding Polycystic Ovarian Syndrome (PCOS) and the Need to Customize Ovarian Stimulation Protocols.

      I invite you to call 702-699-7437 or 800-780-7437 and set up a one hour Skype consultation with me to discuss your case in detail.

      I also suggest that you access the 4th edition of my book ,”In Vitro Fertilization, the ART of Making Babies”. It is available as a down-load through http://www.Amazon.com or from most bookstores and public libraries.

      Geoff Sher

    • Tina says:

      Case History:
      2 Failed IVF cycles at age 25 in from same facility and 1 Failed IVF at age 26 from new facility. Reason for infertility being tubal with bilateral hydrosalpinx, tubal ligation done prior to IVFs, no sperm issue. Every cycle all embryos arrested, cycle #1 I stimmed with Follistim, low dose hcg and Ganirelix. 22 follicles were retrieved, 15 mature and 6 fertilized no ICSI, all embryos arrested. Cycle # 2 I stimmed with Bravelle, Menopur and Ganirelix. 16 follicles were retrieved, 12 mature and 6 fertilized with ICSI, all embryos arrested. This year, went to a new facility, stimmed with Gonal-F, Menopur and Cetrotide. 23 follicles were retrieved, 11 were mature and 6 fertilized with ICSI again all embryos arrested. Would love any input or thought you have on my history, thank you!

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