It was once said that challenges are meant to be met and overcome and this holds true for modern medicine pretty well. In the field of reproductive medicine it is no different.
Dr Stavros Natsis, Head fertility specialist at Gennima IVF, during this #IVFWEBINARS, talks about some cases which seemed to be pretty obvious from the beginning but turned out to be complete miracles. He starts with an uplifting message: never lose your hope and remember that there is always some light at the end of the tunnel.
The first case Dr Natsis talks about is a young couple (both 39 years old) who experienced 8 years of natural pregnancy attempts that resulted in 5 miscarriages (with no heartbeat detected at – usually – 6 weeks of pregnancy). Their karyotype test results were completely normal. The main problem was the fact that the woman had a condition called complete bicornuate uterus which was detected in 2013. It is a type of uterine duplication anomaly which is characterised by the presence of the septum starting from the fundus of the uterus and reaching up to the cervix. Although the patient had 3 attempts of hysteroscopy to dissect it, none of them was successful. This was one of the reasons why the embryos did not implant – there was not a healthy area for the placentation. Additionally, the patient had low levels of both AMH and FSH.
Based on the patient’s medical history, doctors at Gennima IVF decided that a metroplasty with hysteroscopy was needed again in order to make sure that the uterine septum would go away. After the dissection of the septum, they wanted to let the patient try for another six months – but not more than that, due to the low AMH levels.
Dr Natsis recalled that in March 2018, the patient underwent the first hysteroscopy (metroplasty) at Gennima IVF and during that procedure, the doctors dissected approximately 70% of the septum. Then in August 2018, the second and final hysteroscopy followed – together with a biopsy of the lining of the womb. The sample was sent to the French lab that Gennima IVF collaborates with, in order to assess the immune system of the endometrium and to decide what sort of medication should be given to support the pregnancy.
Following the second hysteroscopy, the patient had a natural conception 3 months later. The pregnancy was closely monitored. The doctors advised the couple to perform a cervical cerclage during the 14th week of the pregnancy. Because of multiple surgeries the patient had undergone, they were afraid that the cervix would be incompetent. Finally, after an uneventful pregnancy, a patient delivered a healthy baby girl. Such a successful ending made the whole Gennima IVF medical team very happy!
The second couple that Dr Natsis analyses in his webinar is an example of recurrent IVF failures, multiple miscarriages and very low ovarian reserve. When they first came to the Gennima IVF clinic, they were 41 years old and had a 3-year history of pregnancy attempts . The woman’s AMH was very low – approximately 0.3 ng. She had IVF short protocol performed three times – she had 2 modified natural cycles with the fertility drug Clomid as well as 10 natural cycles with no medication at all. The results were: 1 miscarriage at the 8th week of pregnancy (although the baby’s karyotype was tested and classified as a normal one) and 3 biochemical pregnancies. A thorough medical screening that a patient was subjected to, revealed that she had a Von Willebrand disease. It’s a condition that impairs the blood clot and puts a patient at an increased risk of bleeding. However, the screening did not reveal any abnormal level of NK cells nor any significant pathology of the endometrium.
During a medical review, the doctors at Gennima IVF found out that the fundus of the uterus had a mild septum. This – in their opinion – could cause some difficulty in the embryo implantation. The treatment plan included a hysteroscopy with creating implantation cuts that would be immediately followed with an IVF treatment. Because of the patient’s age and her low AMH level, there was not much time to wait for a natural conception. There was also the possibility of the endometrium biopsy taken into account – in order to determine the immunology profile and the post-implantation treatment.
In January 2019, the patient underwent the hysteroscopy during which the small septum was dissected and the implantation cuts were created. There was also a biopsy performed and the sample was sent to the lab in France (as in the previous case study). The biopsy result showed abnormal uterine cytokine equilibrium as well as increased uterine Natural Killers. It is important to mention here that the patient had had an evaluation of peripheral blood NK cells done in one of the previous clinics – which turned out to be normal. According to Dr Natsis, it only proves that this kind of test – although vastly popular – does not have any clinical significance.
Based on the biopsy results, the doctors created the post-implantation treatment protocol for the patient. In February 2019, the patient underwent a modified natural cycle with Clomid – especially helpful in case of patients with low ovarian reserve. 2 eggs were collected and fertilised and one good quality day 3 embryo was transferred. The pregnancy test was positive. Again, the doctors performed a cervical cerclage in the 14th week of the gestation.
Dr Natsis says that the patient could not believe she was pregnant and consequently needed a lot of psychological support. Finally, she delivered a healthy baby boy at 39 weeks of pregnancy through a C-section.
The third case Dr Natsis discusses is extraordinary. The couple he treated had experienced approximately 30 IVF attempts – the largest number they have ever had at Gennima IVF clinic! When Dr Natsis met them, they were only 37 years old and already had 8-year experience of IVF attempts. The female patient underwent 6 IVF cycles with short protocol and 25 natural cycles – and the only result was one miscarriage in the 9th week of pregnancy and 2 biochemical pregnancies (!).
The review of medical notes revealed that the patient had two surgeries for possible endometriosis (laparoscopic surgery) as well as double hysteroscopy – in order to deal with her polyps and endometrial adhesions. She also had low ovarian reserve. Another issue the doctors had to help with was the unsatisfying result of the male partner’s sperm analysis, meaning both low count and low motility. Additionally, just like the previous two case studies the hysteroscopy conducted at Gennima IVF revealed the presence of a small septum.
Due to the 30 unsuccessful IVF attempts, the doctors assumed the patient had a very serious problem with the quality of her eggs and they suggested egg donation. However, the patient opted for the last final attempt with her own eggs – and the doctors agreed with her wish.
In November 2014, a hysteroscopy was conducted and during that procedure the uterine septum and adhesions were dissected. Three months later, the doctors collected 3 eggs during the short IVF protocol and 2 out of those 3 eggs were fertilised with ICSI. On day 3, two good quality embryos were transferred and the woman became pregnant. Similarly to the previously mentioned patient, she needed a lot of psychological support during her pregnancy as she could not believe she was pregnant. In December 2015, she gave birth to a healthy baby boy.
This case perfectly shows that women who have multiple medical conditions can become pregnant if they get right treatment. Dr Natsis recalls that the patient was 44 years old (with 7 years of attempts) when she came to Gennima IVF clinic for the first time. In her history, she had one natural conception but the pregnancy had to be terminated – the child had a genetic syndrome which was picked up in a nuchal translucency scan. Additionally, the woman’s BMI was 37 at that time, she suffered from hypertension and diabetes and she had undergone 2 strokes. Her history of pregnancy attempts included clomiphene stimulations and IVF-ICSI. She also had a hysteroscopy with polyps removal performed and her partner suffered from obstructive azoospermia. While reviewing the patient’s hysteroscopy DVD, Dr Natsis and his colleagues found a small septum in the uterus, too.
The doctors’ plan was to assure the perfect state of the womb lining in order for it to accept the embryos. Firstly, they asked the patient to adopt a more healthy lifestyle and lose weight. Secondly, the woman was reviewed by a cardiologist, endocrinologist and neurologist to make sure that she would go through pregnancy without problems. The patient decided on egg donation.
The doctors performed a hysteroscopy to dissect the uterine septum in March 2018 and six months later (in September 2018), the perfect phenotypically matched donor was found. The donor produced sufficient number of eggs in the second cycle and 4 of them were fertilised with the sperm of the woman’s partner – through the use of ICSI. The embryos were cultured until day 5 in a modern incubator called Embryoscope+, allowing for non-invasive prenatal screening and helping to choose the embryos with the best chances of success. Two embryos were transferred and the woman got pregnant successfully. After a closely monitored but uncomplicated pregnancy, she delivered a completely healthy baby girl and now she is considering a second child.
The last case that Dr Natsis deals with involves severe male infertility. The couple that came to Gennima IVF clinic was a 27-year old girl and a 50-year old man who suffered from azoospermia – the condition in which a man does not produce any spermatozoa in his semen. When discussing the treatment plan with the couple, the doctors suggested a series of sperm analysis. The intention was the following: if during such a screening some spermatozoa were identified, they would be cryopreserved for later use. If no sperm was to be identified, the doctors would decide to do a testicular biopsy.
The sperm analysis conducted in February 2018 showed 5 healthy and moving spermatozoa – the specimen was cryopreserved. The sperm analysis was repeated a month later and then 8 more spermatozoa was found and cryopreserved as well. Dr Natsis notes here that during both tests, the embryologists had to process each sample for unbelievably long time – 12 hours! However, thanks to their effort, the man was spared an uncomfortable and painful testicular biopsy.
After the sperm was secured, the woman underwent the so-called ‘short protocol’ and 7 eggs were collected. One of them was fertilised through ICSI with thawed specimen and after 3 days, one good quality embryo was transferred. Again, the pregnancy was classified as uncomplicated and it finished with the delivery of a healthy baby boy.
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Summing up, Dr Stavros Natsis addresses all the couples who are now in the middle of IVF treatments – especially those experiencing multiple failures. Firstly, they should never lose their hope and never give up looking for possible solutions. In case of repeated failures, it’s advisable to search for a new clinic that may look at their medical history from the ‘fresh’ perspective. At most clinics, multidisciplinary meetings are held during which many fertility experts meet and try to tailor the clinic services to the patients’ needs. Dr Natsis also believes in the use of the latest technologies, like e.g. EmbryoScope+, and the fertility education of the patients. The latter is helpful in making them understand what is needed and necessary to be done. The cooperation between doctors and patients is crucial – it is much more valuable than just following the medical instructions blindly.
Dr Stavros Natsis finishes with a great quote by Nelson Mandela:
- Questions and Answers
It always seems impossible… until it’s done. A perfect message and an ideal beacon of light in the darkness – for all those facing fertility issues every day.