Let’s Talk About ICSI (Intracytoplasmic Sperm Injection)
My husband and I are about to make our embryos, and we are so excited to be entering this phase of our journey. Last year, we made our sperm donations at our IVF clinic, and you can read more about that experience in a previous article (https://www.babymoonfamily.com/original-articles/clinic-masturbation). More recently, we went through the process of choosing our egg donor (https://www.babymoonfamily.com/original-articles/choosing-egg-donor), and now our egg donor’s retrieval is scheduled for July 4th (Go, America!).
When finalizing the clinic consents for the embryo creation, we were informed that our reproductive endocrinologist prefers intracytoplasmic sperm injection (ICSI) for fertilization with frozen sperm. So, in this article, I wanted to do a review of ICSI, including the following:
What is ICSI?
How is ICSI performed?
When is ICSI used?
Risks of ICSI
ICSI in the context of our journey
What is ICSI?
(1)
ICSI is an in vitro fertilization (IVF) procedure in which a single sperm cell is injected directly into the cytoplasm of an egg, as shown in the figure above. This procedure results in the formation of an embryo, which can then be implanted into the uterus.
The technique was developed and first performed by Gianpiero Palermo in the Center for Reproductive Medicine at the Vrije Universiteit Brussel (2). The first embryo creation through ICSI occurred in 1990 (3), while the first birth involving ICSI took place on January 14, 1992 (4).
ICSI allows a single sperm to fertilize an egg, as opposed to the 50,000 to 100,000 sperm needed to naturally fertilize an egg. Because there is no ‘natural selection’ for the sperm who ‘wins’ and fertilizes the egg in ICSI, it’s important to choose the ‘right’ sperm.
How is ICSI Performed?
The first step in ICSI involves selecting the sperm for injection. There are several methods that are used to identify the ‘best’ sperm, and one of the more modern techniques involves a microfluid chip called a Zymot ICSI chip (https://www.zymotfertility.com/). The sperm is placed on the chip, which mimics the environment of the vagina in order to identify the sperm with the best motility, morphology (shape), and less DNA fragmentation. Other methods use magnetic particles or hyaluronic acid to identify mature, quality sperm for implantation (5).
Eggs and sperm for ICSI can be thawed or retrieved fresh. In our case, the sperm will be thawed and the eggs will be fresh, and studies show that success rates with ICSI are similar with fresh and thawed sperm (6). When the egg and sperm are ready, the injection can take place. The procedure is done under a microscope using micromanipulation devices. A holding pipette stabilizes the mature oocyte with gentle suction applied by a microinjector. From the opposite side a thin, hollow glass micropipette is used to collect a single sperm, having immobilized it by cutting its tail with the point of the micropipette. The oocyte is pierced through the oolemma and the sperm is directed into the inner part of the oocyte (cytoplasm).
The fertilized eggs are then observed in the lab as they develop into blastocysts. These will then undergo pre-implantation genetic testing (PGT) to ensure that only embryos with the correct amount of chromosomes are selected for implantation.
When is ICSI used?
ICSI was developed to help reproduction with male-factor infertility. This makes sense given that it removes a lot of the ‘heavy lifting’ that sperm need to do in order to fertilize an egg. ICSI sperm do not need to swim and literally fight off hundreds of thousands of other sperm to enter the egg. Therefore, sperm with poor motility, shape, and/or development can still be used to fertilize an egg via ICSI.
However, the use of ICSI has increased dramatically for non-male factor infertility. In the United States, the use of ICSI for all indications increased from 36.4% in 1996 to 76.2% in 2012, with the largest increase (from 15.4% to 66.9%) occurring in cycles with non-male factor infertility (7).
The rationale for this increased use of ICSI is to avoid fertilization failure from ‘unexplained infertility.’ I have previously written about the process of egg donation (https://www.babymoonfamily.com/original-articles/egg-donation-procedure), and it is not something that would be ideal to do multiple times. Therefore, IVF clinics want to do everything possible to maximize the chances of successful embryo creation, and so they often rely on ICSI.
The American Society of Reproductive Medicine (ASRM) published a great review of this topic, and they reached the following conclusions (8):
ICSI without male factor infertility may be of benefit for select patients undergoing IVF with preimplantation genetic testing (PGT) for monogenic disease and previously cryopreserved oocytes.
The additional cost burden of ICSI for non-male factor indications, where data on improved live-birth outcomes over conventional insemination are limited or absent, must be considered.
Additional studies also demonstrate support for IVF-ICSI as the recommended treatment for couples with cryopreserved sperm, especially when the cryopreserved sperm is the only viable sample as the male has undergone chemotherapy or surgery due to cancer (9).
Risks of ICSI
With ICSI, there is a risk that a small percentage of the eggs (usually less than 5%) can be damaged as a result of the needle insertion (10). There are studies that suggest birth defects are increased with the use of IVF in general, and ICSI specifically, though different studies show contradictory results. The University of California, San Francisco Medical Center and other reproductive centers state that ICSI increases the overall risk of having a baby with a chromosomal abnormality in the X or Y chromosomes to about 0.8%, or 8 per 1000, which is four times the average seen with spontaneous conception (10). Abnormalities on these chromosomes can lead to increased risk of miscarriage, heart problems, learning disabilities, or infertility for the children later in life.
ICSI in the Context of Our Journey
ICSI is another incredible technology that allows for assisted reproduction in the face of infertility. The evidence for ICSI suggests that the cost and complexity make it unnecessary for routine IVF, but there is very little evidence specific to a situation such as my husband and me: Two healthy sperm donors proceeding with a young, healthy egg donor.
I think this is one of the areas of research that hopefully will continue to evolve with the growing interest in ART for queer intended parents (IPs). However, I believe that our geographical constraints as international IPs and the reproduction logistics of an egg donor and gestational carrier (GC) means that our IVF clinic wants to do everything possible to optimize for embryo success. If this means increased costs for utilizing ICSI, then they will do that. Fortunately, our contract and ‘peace of mind’ program do not charge us extra for this procedure, but that would be something to consider if you have a different arrangement with your IVF clinic.
I would be lying if I didn’t have some concerns about the data demonstrating miscarriages and birth defects related to ICSI, but this process - and life in general - is not without risks. There are so many things that can go wrong, but most of the time, the process does go well. Also, based on our cryopreserved sperm and complex reproductive logistics, ICSI does seem like the best option for our embryo creation.
We are looking forward to a great egg retrieval, ICSI fertilization, and optimal PGT embryos in the next few weeks. Then we can begin the fun of matching with a GC and trying to get pregnant.
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