Year : 2019 | Volume
: 12 | Issue : 2 | Page : 75--77
From the Editor's Desk
Dr. Patil's Fertility and Endoscopy Clinic, Bengaluru, Karnataka, India
Dr. Madhuri Patil
Dr. Patil's Fertility and Endoscopy Clinic, Bengaluru, Karnataka
|How to cite this article:|
Patil M. From the Editor's Desk.J Hum Reprod Sci 2019;12:75-77
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Patil M. From the Editor's Desk. J Hum Reprod Sci [serial online] 2019 [cited 2020 Jan 28 ];12:75-77
Available from: http://www.jhrsonline.org/text.asp?2019/12/2/75/260503
Polycystic ovary syndrome (PCOS) is a complex clinical syndrome due to multigene environmental interaction resulting in hormonal changes which are exacerbated by obesity. Associated with hyperandrogenemia, which results in hirsutism and acne and can also affect folliculogenesis resulting in menstrual irregularity. There are also hyperinsulinemia and insulin resistance (IR) with higher risk of type II diabetes and metabolic syndrome, which increase the cardiovascular risk apart from its effect on folliculogenesis. Metabolic syndrome should be assessed clinically by the presence of acanthosis nigricans and truncal obesity. Fasting lipid and 75-g oral glucose tolerance test with or without HbA1C is a must. Increased visceral adiposity is seen across all categories of body mass index, which exerts its effect on insulin resistance, hyperglycemia, and dyslipidemia in paracrine and endocrine manner via secretion of number of molecules, some of which are markers of inflammation. Important links are seen between total and regional body fat, IR, low-grade chronic inflammation, and circulating sex hormones. It has also been seen that increased abdominal adiposity contributes to inflammatory load in PCOS and its development may be controlled by severity of hyperandrogenism. In an original article which compared body composition, metabolic characteristics, and insulin resistance in obese and nonobese women with polycystic ovary syndrome showed that both the groups had more visceral obesity, IR, and metabolic syndrome. This group concluded that it is not only the obese but also the nonobese should be advised lifestyle modification to prevent metabolic complications.
There are several genes involved in oogenesis and folliculogenesis, and any change in the genotype can affect the ovarian function which can result in poor response to ovarian stimulation, polycystic ovary syndrome (PCOS), and premature ovarian insufficiency (POI). It can also affect the oocyte and embryo quality, gene expression profiling of cumulus cells, proteomics and metabolomics, resulting in failed embryo implantation and recurrent pregnancy loss (RPL). In a study from Jordon, they looked at seven single-nucleotide polymorphisms (SNPs) in NOBOX gene in women with poor ovarian response and compared the results with fertile females. NOBOX is a homeobox gene localized to chromosome 7q35 and is oocyte specific, expressed from the primordial follicle through metaphase II oocytes. It promotes primordial follicle activation and has been shown to promote oocyte and follicle growth beyond the primordial follicle stage. It is a conserved homeodomain transcriptional regulator that is exclusively expressed in the oocytes but not in the surrounding pregranulosa cells. NOBOX mutations have been identified in certain population with POI. This study did not find any link between poor ovarian response and seven previously studied SNPs in NOBOX gene. They concluded that only monomorphic genotype of the NOBOX variant was found in Jordanian women.
The four most common causes of amenorrhea are polycystic ovary syndrome, hypothalamic amenorrhea, ovarian failure, and hyperprolactinemia. Ovarian failure apart from exposure to chemo- and radiotherapy is a result of chromosomal abnormalities such as gonadal dysgenesis due to chromosomal abnormalities of Fragile X syndrome. A retrospective study from the Department of Cytogenetics, National Institute of Immunohaematology, Mumbai, looked at the chromosomal aberrations in primary amenorrhea. The incidence of cytogenetic abnormalities in primary amenorrhea reported in this study was 24.7%. Thus, all patients with amenorrhea should be subjected to cytogenetic evaluation for the correct diagnosis which will help both in counseling as well as management.
In vitro fertilization (IVF) with embryo transfer (ET) is most effective option and should be the first line of treatment in the management of endometriosis-associated infertility in women over 38 years, with Stage III/IV endometriosis, in those with a significant adhesive or tubal disease, and in couples with a significant male factor. Poorer success (implantation rate and pregnancy rate [PR]) is seen with IVF with increase in severity of endometriosis. The endometriosis fertility index (EFI) possesses predictive power for a successful pregnancy with natural intercourse or intrauterine insemination in infertile patients. EFI can give a realistic assessment of PRs for up to 3 years after laparoscopic surgery, especially in women who do not have access to IVT-ET. It is also noted that after 3 years, very few pregnancies occur regardless of EFI score. Thus, EFI helps counseling women with endometriosis on the current fertility potential and the prognosis for non- assisted reproductive technology (ART) conception. Neha Negi from Delhi evaluated 123 patients for EFI and concluded that laparoscopy apart from providing significant symptomatic relief helps in estimation of EFI, which is a good predictive tool for occurrence of non-ART pregnancies. This study showed a statistically significant positive correlation of EFI with pregnancy outcome, PRs being better with higher the EFI score.
Serum anti-Mullerian hormone (AMH) is a good ovarian reserve marker and correlates with severity of PCOS and precisely with the severity of hyperandrogenism, oligo-anovulation/amenorrhea, and polycystic ovarian morphology. The threshold value of 4.86 ng/ml has a sensitivity of 92% and a specificity of 97% for diagnosing PCOS. In PCOS, the number of all growing follicles is increased, resulting in a marked increase in both serum AMH level and antral follicle count (AFC), but AMH is considered as more sensitive marker to define follicle excess than AFC as it appraises more follicle classes. There were several concerns regarding the performance of AMH assay in the past. Results can be affected by improper storage of samples and handling, widely variable AMH measurements made by the various AMH assays, even when using the same clinical sample and lack of standardization of assay. AMH level is not only the best biochemical marker of ovarian function but actually also contributes to PCOS pathogenesis. Nalini Mahajan et al. looked at AMH threshold for diagnosis of PCOS in women of reproductive age-bearing Indian ethnicity using the automated AMH assay and concluded that a serum AMH concentration of >5.03 ng/mL may help facilitate diagnosis of PCOS in women of Indian origin. Although AMH seems to be a good marker for diagnosis of PCOS, the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018 has said that serum AMH levels should not yet be used as an alternative for the detection of PCOM or to diagnose PCOS.
A male infertility factor is often defined by abnormal semen parameters but may be present even when the semen analysis is normal. Thus, it is important for an infertility practitioner to know the advantages and limitations of various laboratory tests in the diagnosis of male infertility. Apart from thorough history taking and physical examination endocrine evaluation, ultrasound, specialized clinical tests on semen and sperm (quantification of leukocytes in semen, tests for antisperm antibodies, DNA fragmentation index [DFI], measurements of sperm creatine kinase and reactive oxygen species), genetic screening and sperm DNA aneuploidy have been used to find the cause. A study published in Italy evaluated the correlation between corrected protein p53 concentration on sperm DNA and male fertility potential. Members of the p53 family are involved with male and female germ cell survival and functionally linked to germ cell apoptosis, which may affect human infertility. Few studies have demonstrated that genetic variants in genes of the TP53 pathway are risk factors for male infertility. This study concluded that evaluation of protein p53 in male infertility may help in identifying reduced fertility with normal semen parameters and could also predict IVF results. There was another study from France which looked at the DFI and sperm decondensation index (SDI) as prognostic markers after ICSI. They observed that SDI was lower when DFI was high and had poor prognostic after ICSI.
In male infertility, a positive correlation has also been seen between deep periodontal disease and subnormal sperm parameters, which suggests that periodontitis may have a role in idiopathic semen abnormalities. Most previous publications have reported a maximum positive correlation between periodontal infection and sperm submotility of all sperm parameters, though one study did not find any correlation between poor periodontal status and male subfertility unless there is presence of genital infection. This makes it mandatory for all patients undergoing andrological examination and attempting to conceive to receive comprehensive oral evaluation with reference to a dentist if necessary. We have an original article by Chethana Chidambar et al., which shows a positive correlation between periodontal status and male infertility.
Progesterone (P4) elevation (PE) on the day of human chorionic gonadotropin (hCG) administration is associated with a decreased probability of pregnancy achievement in fresh IVF cycles, and therefore, it is highly recommended to closely monitor ovarian stimulation cycles by measuring serum P4 at hCG trigger. Detrimental threshold values of P4 are lower for low responders and higher for high responders. Adverse effect of PE does not seem to be present in frozen–thawed and donor/recipient cycles. Freezing all embryos and transfer in a subsequent artificial endometrial preparation cycle is recommended in case of P4 rise in a fresh cycle. In an original article by Nagaraja N et al., there was no statistical difference in the clinical PRs despite PE, and therefore, they concluded that the decision to defer ET should not be done only for PE.
Preimplantation genetic testing for aneuploidies (PGT-A) is done to increase the live birth rate (LBR) by transfer of euploid embryos in women with advanced maternal age, recurrent implantation failure, RPL, and severe male factor and for embryo selection. Embryo biopsy can be done either on day 3 (blastomere) or day 5 (trophectoderm cells [TE]). Two problems associated with PGT-A when either blastomere or TE biopsy are that there is a risk of false-positive diagnosis due to the presence of mosaicism and may result in the discard of clinically competent embryos. The blastomere and TE biopsy may not reflect the true genetic status of inner cell mass (ICM), and therefore, the reliability of PGT-A is still highly controversial. In an original article, comparison of embryonic aneuploidy with preimplantation genetic screening was done between age- and indication-matched Spanish and Indian women. This study concluded that the aneuploidy rate is similar in women from both countries and a TE biopsy is more superior to blastomere biopsy on day 3 with a higher PRs. This is probably due to the increased available time for embryos for self-correction.
Slow freezing, rapid freezing, and ultrarapid freezing (i.e., kinetic vitrification) are conventional cryopreservation methods, whereas cryoprotectant-free vitrification is the new method. Various factors during the freezing process, including sudden temperature changes, ice formation, and osmotic stress, have been proposed as reasons for poor sperm quality postthaw. It has been observed over the years that motility, plasma membrane functionality, acrosome integrity, and overall viability of spermatozoa postthaw typically decrease in contrast to the prefreeze state. Moreover, epigenetic and proteomic modulation of sperm and transgenerational effects of sperm freezing have not been studied. Some recent publications have shown high viability of viruses, bacteria, mycoplasmas, and fungi after cryoprotectant-free cryopreservation in culture medium and even in distilled water. In this, we have a randomized controlled trial on comparison of slow-freezing versus permeable cryoprotectant-free vitrification of abnormal semen sample. This article has shown comparable results both with slow-freezing and permeable cryoprotectant-free vitrification. Although permeable cryoprotectant-free vitrification decreases the negative effect of freezing on the sperms, it still needs further validation before it can be used routinely for cryopreserving semen sample.
There have been very few studies which have looked at the effect of large aggregates of tubular smooth endoplasmic reticulum (aSER) after conventional IVF. Most studies have shown no difference between aSER-positive oocytes and non-aSER oocytes in the fertilization rate or the rate of embryo development on day 3 and day 5–6. There was also no difference in the PR and clinical PRs between the two groups. However, SERT-MII oocytes had lower rates for both blastocysts and good-quality blastocysts' development. This issue has a study which looks at the LBRs in IVF cycles with oocytes containing smooth endoplasmic reticulum aggregates and normal oocytes and found that there was no difference. However, there was a reduction in the LBR if >50% of the oocytes were aSER positive.
Singleton pregnancies following ART are at a higher risk of adverse perinatal outcomes compared to spontaneous conceptions, and this increases in the presence of multiple gestation. Increased risk of preterm birth (PTB), low birth weight (LBW) and small for gestational age in singletons following transfer of multiple embryos versus single ET and in singleton live births with initial multiple gestational sacs. However, there was no significant difference in the risk of PTB or LBW in singleton live births with an initial single gestational sac. In a study from South India, there was no significant difference in the perinatal outcome in singleton pregnancies following vanishing twin phenomenon as compared to singleton pregnancies with an initial single gestational sac following ART. Apart from this, we have a case report on “Mixed gonadal dysgenesis: A diagnostic challenge.”