CK was 38 years old and had been dealing with secondary infertility for many years. She conceived once in the distant past in a prior relationship but terminated that pregnancy.

While being treated by a prior physician, Dr. A, CK was diagnosed with blocked fallopian tubes (both sides). Not only were the tubes blocked, the left tube was full of fluid, a condition called “hydrosalpinx.” The concern about this condition is that this fluid collecting in the Fallopian tube, which is probably natural tubal fluid, eventually turns toxic and may leak back into the uterine cavity. At this point, CK’s fertility issues were attributed to “poor quality fallopian tubes” and Dr. A recommended IVF, and prior to treatment, Dr. A performed a laparoscopy to clip the fluid filled tube near the uterus so that “toxic” fluid would not spill back into the uterus.

Once CK recovered, she underwent an “antagonist” IVF protocol: estrogen prime, 425U of FSH +HMG injections for 7-10 days, 7-10 days of low dose HCG injections, antagonist injections for 3-5 days, an Ovidrel injection to release the eggs, a general anesthesia egg retrieval, and a day 5 blastocyst transfer of the 1 embryo produced during her cycle (from 8 eggs that were retrieved). Unfortunately, the transfer was not successful. Based on her age, CK had a 30-35% chance of getting pregnant, so the reasonable thing to do was try again.

CK did not feel well from her first cycle so she looked for an alternative protocol which led her to Dr. B who recommended that they try a Letrozole minimal stimulation protocol: Letrozole for 7-10 days, FSH (150 U x 6 injections), an Ovidrel trigger, doxycycline, and a general anesthesia retrieval. 8 eggs were retrieved again, but this time, from those eggs, 3 embryos were produced. Dr. B decided to do a fresh transfer for two of the embryos and freeze the third for a frozen embryo transfer later, if necessary. CK was put on a regimen of dexamethasone, progesterone oil muscle injections, and had a day 3 fresh transfer of 2 embryos, which was unsuccessful. The frozen blastocyst, unfortunately, did not survive the thaw and CK was back to square one.

This all led CK to me.

After reviewing her history, I had the following thoughts:

• If this was merely a tubal issue, why wasn’t there implantation with either of her transfers?
• Why was there only 1 blastocyst in her first cycle when the third-best embryo from her second cycle made it to blastocyst (assuming that the two best embryos were transferred fresh on day 3)?
• Why bother with a day 3 transfer when CK a had a blastocyst in her first cycle?
• Why bother repeating a fresh transfer when it failed the first time?

And the following suggestions:

• Minimal stimulation IVF. Since CK was relatively young and had shown that she could produce good quality embryos (i.e. blastocysts), why not try to use the least amount of medication to make these embryos?
• Earlier retrieval. In a traditional IVF cycle, there is a tendency to let a leading follicle grow larger than is ideal to allow more of the smaller follicles reach a larger, retrievable size. The leading follicle is essentially, in this case, sacrificed. The philosophy behind Japanese IVF, however, posits that the leading follicles are the ones that are the most likely to lead to healthy pregnancies. Sacrificing this leading follicle means that you are sacrificing the egg that would have given you the best chance for success. I suspect that this may have occurred in CK’s first cycle, which is why she was able to get only 1 blastocyst out of the 8 eggs that were retrieved.
• Blastocyst culture. Day 3 embryos are not nearly as predictable as blastocysts, so you often need to transfer more than 1 to achieve a reasonable success rate. However, transferring more than one embryo introduces risks and complications associated with multiple implantation, and, in failure, you are uncertain if the failure is due to embryo or environment. Using blastocysts will give you more information (and avoids the multiple implantation risks/complications).
• Freezing. Since CK already failed using fresh transfers twice, it made sense not to recommend this route again. Traditional IVF cycles are stressful on the body and mind. Freezing embryos allows us to be more flexible with the timing of a transfer so that we can schedule transfers to coincide with optimal uterine environments.
• Hysteroscopy. I was suspicious because of CK’s lack of implantation. If CK continued to produce blastocysts at a high rate, I thought that there may be an underlying endometrium issue which could have been associated with her prior pregnancy termination or an ascending infection which could have contributed to the blockage of her tubes.

We moved forward with this plan. I chose a “classic” minimal stimulation protocol using Clomid. Letrozole, which she with Dr. B, is a tricky medicine to use and I prefer to save it for select situations. CK did Clomid for 5-7 days, FSH (150 U x 3 days only), a GnRH agonist trigger, and had her egg retrieval under local anesthesia. This resulted in 6 eggs, 4 of which progressed to blastocysts! This made me feel even more strongly about an environment issue. We froze the 4 blastocysts using vitrification (of course) and proceeded with our Hysteroscopy and prepared for a frozen embryo transfer.

For frozen embryo transfers, I prefer natural cycle transfers where the patients’ own hormones develop the environment. In artificial cycles (also known as hormone replacement cycles or HRT), I often worry that the medicines will overwhelm many of the subtleties of a natural, ideal environment. The downside of natural cycle transfers is that you skip quite a number of cycles. In CK’s case, it was 3. CK admitted that she was going through a particularly stressful period at work and it seemed to be reflected in her cycles with irregular ovulations and thin linings. Although I offered her the opportunity to use hormones, she preferred letting her body tell her when the time was right. During her 4th cycle, CK’s work stress had significantly decrease and this was reflected by a normal ovulation length and an ideal 9mm lining. Her progesterone level was a little low so we supplemented her with a little bit of vaginal progesterone. I performed a single embryo transfer under transvaginal ultrasound guidance (I don’t understand doing blind transfers or transabdominal ultrasound transfers since the uterine lining is usually measured transvaginally anyway). 1 week later, CK was pregnant!

Japanese IVF had allowed CK to:

• Collect more eggs safely and comfortably.
• Confirm her embryo quality, throwing suspicion on a non-embryo cause for her failure.
• Save her embryos safely to use in either the immediate or distant future.
• Find a perfect time and environment for her embryo transfer.
• Minimize the risks of multiple implantation.

I have since graduated CK to her Obstetrician and I have 3 more embryos waiting for her in case she wants to extend her family in the future.

‍