Case Report: Recurrent IVF Failure due to Uterine Adenomyosis and Intrauterine Fibroid Polyps, Requiring Gestational Surrogacy

Linda (43y) and her husband Graham (49y) had been trying to conceive for 6 years. She had been pregnant once before in 1993. This pregnancy, which was initiated in a previous relationship was aborted, without subsequent complications. Linda had been having regular ovulatory menstrual cycles. Her general health was excellent but her family history was positive for amyotrophic lateral sclerosis (AML).

In 2016 Linda underwent a hysteroscopic myomectomy for the removal of a small fibroid polyp. A follow-up hysteroscopy done the following year, revealed her uterine cavity to be normal. In 2018, she was diagnosed with diminished ovarian reserve-DOR (AMH=0.08ng/ml and her basal [FSH} was 17MIU/ml).

Graham was fertile. He had excellent sperm parameters.

Between 2017 and 2019, the couple had undergone 6 cycles of egg retrieval (ER) with intracytoplasmic sperm injection (ICSI). A total of 12 blastocysts had been generated. These had all been subjected to preimplantation genetic testing (PGT). Later in 2017, Linda, had a single (1) euploid blastocyst thawed and transferred to her uterus by frozen embryo transfer (FET) but did not conceive. She presently has 1 remaining banked, euploid blastocyst.  All the rest (10) were complex aneuploid and were discarded. In September of 2018, Linda underwent hormonal preparation for a second FET attempt. The transfer was canceled because she was found to have a significant and persistent collection of fluid in her uterine cavity, had a thin endometrial lining and there was also a suggestion of a surface lesion in her uterine cavity. Uterine magnetic resonance imaging (MRI) was thereupon performed, and this revealed a 2 cm fibroid polyp protruding into the uterine cavity as well as the presence of extensive uterine adenomyosis,

Upon discussion, the couple insisted that since they under no circumstances, were willing to undergo another ER or ever use of donor eggs/embryos, they wanted their only remaining blastocyst to have the best possible chance of propagating a viable pregnancy.  Upon learning that Linda had a healthy and close, younger sister who had previously successfully conceived and delivered 3 full-term babies, I suggested that the couple approach her to serve as their gestational surrogate. The couple subsequently approached Linda’s sister who readily agreed to serve in this capacity. This treatment will shortly take place.

I intend to follow this couple and will report on their progress as treatment is implemented


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ADDENDUM: General concepts Relating to Gestational (IVF) Surrogacy:

Gestational (IVF) surrogacy involves the transfer of one or more embryos into the uterus of a surrogate, who provides a host womb and carries the baby to term, but does not contribute genetically to the baby. Typically, the intended mother provides the eggs and her partner (the intended father) provides the sperm. However, at times eggs and/or sperm may be derived from gamete donors. While ethical, moral, and medico‑legal issues still apply, IVF surrogacy appears to have gained social acceptance. We offer IVF surrogacy as an option at most SIRM programs.

Candidates for IVF surrogacy can be divided into two groups: (a. women who are not capable of carrying a pregnancy to full term due to: their uterus having been surgically removed (hysterectomy), diseases of the uterus, or congenital absence of the uterus (from birth) and, (b. women who have been advised against undertaking a pregnancy because of systemic illnesses such as diabetes, heart disease, hypertension, etc.

As in preparation for other assisted reproductive (AR) techniques, the biological/intended parents, the surrogate and/or donors undergo a thorough clinical, psychological, and laboratory assessment prior to embarking on the process. The purpose is to exclude sexually transmitted diseases that might damage eggs, sperm and embryos, or be carried to the surrogate with embryo transfer. They are also counseled on issues faced by all IVF participants such as the possibility of multiple gestation, miscarriage and ectopic pregnancy.

All legal issues pertaining to custody and the rights of the biological parents and the surrogate should be discussed in detail and the appropriate consent forms completed following full disclosure. We recommend that the surrogate and biological/intended parents get separate legal counsel to avoid any conflict of interest that could arise were one attorney to counsel both parties.

Selecting a Surrogate

Couples with the necessary financial resources will usually retain a surrogacy agency to find a suitable IVF surrogacy candidate. We direct our patients to reputable surrogacy agencies who have access to quality surrogates. Because the surrogate gives birth, it is rarely possible or even realistic for her to remain anonymous.

Since recruiting a gestational surrogate from an agency can be very expensive, many infertile couples who qualify for IVF surrogate parenting solicit the assistance of empathic friends or family members to act as surrogates.

Other couples independently seek surrogates by advertising in the media.

Screening the Surrogate

Once the surrogate has been selected, she will undergo thorough medical and psychological evaluations, including:

  1. Cervical cultures and/or blood tests to screen for infection with sexually transmitted bacteria such chlamydia, ureaplasma, gonococcus and syphilis or viruses such as cytomegalic virus, HIV, HTLV, and hepatitis.
  2. A variety of blood‑hormone tests, such as the measurement of plasma prolactin and thyroid‑stimulating hormone (TSH) and tests to ensure that the surrogate is immune to the development of rubella (German measles).
  3. 3. Physical evaluation
  4. Psychological assessment

When friends or family members serve as IVF surrogates they should be carefully assessed to ascertain whether they might have been coerced to participate. This is especially important when a young family member is being recruited.

The surrogate should also be counseled on issues such as risks and consequences of multiple pregnancies. Such discussions should include agreement on the number of embryos to be transferred and the delicate issue of selective pregnancy reduction , in the event of a high order multiple pregnancy (triplets or greater).

The surrogate should visit with her designated IVF physician who should take her medical history and perform a thorough physical examination. Thereupon she should have a full consultation with the nurse coordinator charged with oversight of her treatment. The coordinator will outline the exact IVF-surrogacy process step by step, will make certain that the surrogate understands that she has full right of access to the clinic staff and that her concerns will be addressed promptly at all times. The surrogate should also be informed that if pregnancy occurs, she will be referred to a qualified Obstetrician for prenatal care and delivery.

Once a viable pregnancy is confirmed by ultrasound recognition of a fetal heartbeat (at the 6th-7th week), there is about an 80% chance that the pregnancy will proceed normally to term. Once the pregnancy has progressed beyond the 12th week, the chance of a healthy baby being born is upward of 90%.

Depending on the quality of medical treatment and ther age of the egg provider (under 39y) and her having normal ovarian reserve, we would anticipate approximately a 40% pregnancy rate every time good quality advanced embryos (expanded blastocysts) are transferred. The birthrate falls with further advancement in the age of the egg provider and with diminishing ovarian reserve. It is important to note that there is no convincing evidence to suggest an increase in the incidence of spontaneous miscarriage or birth defects as a direct result of IVF surrogacy.

If the surrogate’s blood pregnancy tests are negative, treatment with estrogen, progesterone and corticosteroids is discontinued, and she can expect to menstruate within four to 10 days. In the event that the pregnancy test is positive, estrogen, progesterone and steroid therapy are continued till the 10th week of pregnancy.

After the evaluation and counseling of both the couple and the surrogate has been completed, the three parties should meet. And, once all the evaluations have been completed, the intended parents will select a date to begin treatment.

Bioethics of IVF Surrogacy

The determination of ethical guidelines has not kept pace with the exploding growth and development in IVF. However, some leaders in the field are working together, sharing experiences and advice, to formulate a code of ethics.

The genetic combination of the male and the female provide two of the essential elements which, along with gestation, are necessary to produce a human being. The two‑out‑of‑three rule basically looks at these three elements: the egg, the sperm, and the gestational component. If at all possible, I recommend that at least two of these three components be contributed by the intended parents. If they can only contribute one, it is important to make every effort not to have the other two contributed by the same person (i.e., the egg provider should not also be the surrogate) as this can cause a variety of problems.

4 Comments

Ashley

Hello Dr Sher i am 37 years old and I have stage 4 Endometriosis and Adenomyosis I have had 5 transfers from ICSI cycles 1 early miscarriage and one ectopic. I have 3 remaining embryos from my last cycle.
I have been on a 3 month down regulation to suppress my Endo. I want to have one more transfer after the down reg. my question is would you recommend I go straight into a FET without a bleed or would you suggest I start HRT on cycle day 2? I am seriously considering surrogacy now If this cycle doesn’t work. Can you make any suggestions .
Many thanks

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Dr. Geoffrey Sher

You should consider the fact that about one third of women who have endometriosis will also have an immunologic implantation dysfunction (IID) linked to activation of uterine natural killer cells (NKa). This will require selective immunotherapy with Intralipid infusions, and/or heparinoids (e.g. Clexane/Lovenox) that is much more effectively implemented in combination with IVF.

More than half of women who have endometriosis harbor antiphospholipid antibodies (APA) that can compromise development of the embryo’s root system (trophoblast). In addition and far more serious, is the fact that in about one third of cases endometriosis, regardless of its severity is associated with NKa and cytotoxic uterine lymphocytes (CTL) which can seriously jeopardize implantation. This immunologic implantation dysfunction (IID) is diagnosed by testing the woman’s blood for APA, for NKa (using the K-562 target cell test or by endometrial biopsy for cytokine activity) and, for CTL (by a blood immunophenotype). Activated NK cells attack the invading trophoblast cells (developing “root system” of the embryo/early conceptus) as soon as it tries to gain attachment to the uterine wall. In most cases, this results in rejection of the embryo even before the pregnancy is diagnosed and sometimes, in a chemical pregnancy or an early miscarriage. As such, many women with endometriosis, rather than being infertile, in the strict sense of the word, often actually experience repeated undetected “mini-miscarriages”.
Women who harbor APA’s often experience improved IVF birth rates when heparinoids (Clexane/Lovenox) are administered from the onset of ovarian stimulation with gonadotropins until the 10th week of pregnancy. NKa is treated with a combination of Intralipid (IL) and steroid therapy: Intralipid (IL) is a solution of small lipid droplets suspended in water. When administered intravenously, IL provides essential fatty acids, linoleic acid (LA), an omega-6 fatty acid, alpha-linolenic acid (ALA), an omega-3 fatty acid.IL is made up of 20% soybean oil/fatty acids (comprising linoleic acid, oleic acid, palmitic acid, linolenic acid and stearic acid) , 1.2% egg yolk phospholipids (1.2%), glycerin (2.25%) and water (76.5%).IL exerts a modulating effect on certain immune cellular mechanisms largely by down-regulating NKa.
The therapeutic effect of IL/steroid therapy is likely due to an ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. IL/steroids down-regulates NKa within 2-3 weeks of treatment the vast majority of women experiencing immunologic implantation dysfunction. In this regard IL is just as effective as Intravenous Gamma globulin (IVIg) but at a fraction of the cost and with a far lower incidence of side-effects. Its effect lasts for 4-9 weeks when administered in early pregnancy.
The toxic pelvic environment caused by endometriosis, profoundly reduces natural fertilization potential. As a result normally ovulating infertile women with endometriosis and patent Fallopian tubes are much less likely to conceive naturally, or by using fertility agents alone (with or without intrauterine (IUI) insemination. The only effective way to bypass this adverse pelvic environment is through IVF. I am not suggesting here that all women who have endometriosis require IVF! Rather, I am saying that in cases where the condition is further compromised by an IID associated with NKa and/or for older women(over 35y) who have diminished ovarian reserve (DOR) where time is of the essence, it is my opinion that IVF is the treatment of choice.

I strongly recommend that you visit http://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
• IVF: Factors Affecting Egg/Embryo “competency” during Controlled Ovarian Stimulation (COS)
• 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 Role of 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)
• Intralipid and IVIG therapy: Understanding the Basis for its use in the Treatment of Immunologic Implantation Dysfunction (IID)
• Intralipid (IL) Administration in IVF: It’s Composition; how it Works; Administration; Side-effects; Reactions and Precautions
• Natural Killer Cell Activation (NKa) and Immunologic Implantation Dysfunction in IVF: The Controversy!
• Treating Out-of-State and Out-of-Country Patients at Sher-IVF in Las Vegas
• Should IVF Treatment Cycles be provided uninterrupted or be Conducted in 7-12 Pre-scheduled “Batches” per Year
• A personalized, stepwise approach to IVF
• How Many Embryos should be transferred: A Critical Decision in IVF?
• Endometriosis and Immunologic Implantation Dysfunction (IID) and IVF
• Endometriosis and Infertility: Why IVF Rather than IUI or Surgery Should be the Treatment of Choice.
• Endometriosis and Infertility: The Influence of Age and Severity on Treatment Options
• Early -Endometriosis-related Infertility: Ovulation Induction (with or without Intrauterine Insemination-IUI) and Reproductive Surgery Versus IVF
• Treating Ovarian Endometriomas with Sclerotherapy.
• Effect of Advanced Endometriosis with Endometriotic cysts (Endometriomas) on IVF Outcome & Treatment Options.
• Deciding Between Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF).
• Intrauterine Insemination (IUI): Who Needs it & who Does Not: Pro’s &
• Induction of Ovulation with Clomiphene Citrate: Mode of Action, Indications, Benefits, Limitations and Contraindications for its use
• Clomiphene Induction of Ovulation: Its Use and Misuse!

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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

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Julieta Alvarez

Dr. Sher, I just wanted to tell you how thankful I am for this informational blog and all your great advice! You are a wealth of knowledge and a huge contributor to the success of many couples dealing with infertility.

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Dr. Geoffrey Sher

That is so very kind of you to say Julieta. BUT the truth is, I get as much out of doing this as readers do. I love doing it. Thank you for following me here!

Geoff Sher

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