Author: Eleni Pap.

Age and spontaneous abortion

Spontaneous abortion or miscarriage, usually during the first trimester of pregnancy (until the 13^th pregnancy week), is a  common complication and refers to a‘spontaneous (without intervention) abortion of the pregnancy before the stage of viability (24^th week)’. There are different types such as complete, incomplete, threatened, missed, septic etc.

The causes are multifacrorial and mostly unknown (>50%). Most probably the result of a combined effect between parental age, genetic, immunological, hormonal and environmental factors. The frequency appears varying and contradicting in the various studies reported, mostly due to the heterogeneity of the methods used and the recording of the results. Overall, 10-15% of clinically diagnosed pregnancies in women of reproductive age (15-45 years), results in spontaneous abortion (miscarriage). However, there are many more missed ones before they are clinically diagnosed, especially when they occur early, before the 7^th week and transvaginal ultrasound examination is not performed. It is estimated that, finally, only 30% of the total conceptions result in the birth of a live baby.

The above results vary also between different groups of women with a steady increase parallel to the age. For instance, while at the age before 30 the rate does not exceed the 10% of the total number of pregnancies, at the age of 45 and after, the rate is 50%  and above!. Women with a previous history of miscarriage have a tendency for recurrence. After two miscarriages the risk of recurrence is double and after three, increases four times!. According to more recent studies, the risk, interestingly, increases significantly also in women who experienced other types of complications in previous pregnancy like premature labor, Cesarean Section, gestational diabetes, low birth weight of the woman herself etc.

Considering the above association between miscarriages and various obstetric complications in previous pregnancy/ies, it has been postulated that a common pathological back-round probably exists which justifies and already is, under further investigation.

In view of these new observations that are emerging recently, women with such a past history, deserve additional follow-up and management.

Another prognostic index of increased risk, regardless of age, is considered to be‘the poor ovarian reserve’ based on the ΑΜΗ levels (Anti-Myllerian Hormone levels). Furthermore, recent retrospective studies have reported that obesity also, increases the risk of both sporadic and recurrent miscarriages. In approximately 2–5% of couples with recurrent miscarriages, one of the partners carries a balanced structural chromosomal anomaly: most commonly a balanced reciprocal or Robertsonian translocation.

The risk of spontaneous abortion (spontaneous abortion) in relation to paternal age.                                                                                              

During the last decades a steady increase of the age of marriage and reproduction in both, women and men, is observed.  Due to increasing decline of the reproductive capability parallel to the advancing age, especially after 35, many of them resort into various, time consuming and costly methods in order to achieve the ‘desired  pregnancy’. The couples, ought to be informed about the additional risks associated with the motherhood as well as with the fatherhood in advanced age (beyond 35). It is statistically proved that the age of the father after 50 represents an independent factor of increased risk for miscarriage. A predisposition often ignored.

In addition, based on recent studies, it has been supported that advanced reproductive age of the man (>40) may be associated with increased  risk of obstetric complications and certain health problems of the neonate e.g. small increase of rare anatomical  malformations (skull, limbs and heart), autism, mental disorders (premature appearance of symptoms of schizophrenia later on), acute lymphoblastic leukemia  etc., probably due to mutations that occur in men of older age. However, this field of research remains limited and contradictory. The risk of these debatable complications is considered small and doubtful, especially in comparison to the advanced reproductive age of the mother, requiring further investigation. Seeking genetic advice though when the age of the man attempting a pregnancy is  40 years of age and beyond, is not meaningless.

Spontaneous abortion, that is unintended loss of early pregnancy before 24 weeks, generally is accompanied by heavy emotional burden, even more so if it re-occurs or when it happens after a prolonged effort to achieve pregnancy due to subfertility. These couples need psychological support and genetic guidance.

Conclusion

• Spontaneous abortion of pregnancy is a common complication with a tendency to re-occur.
• It is directly related with the age of the mother as well as with the age of the father, to a lesser degree.
• There is evidence that spontaneous abortion shares common pathological back-round with other pregnancy complications.
• Psychological support and genetic counselling are indicated.

Literature

Royal College of Obstetricians and Gynaecologists. The Investigation and Treatment of Couples with Recurrent First and Second-trimester Miscarriage.  Green-top Guideline No. 17, April 2011.

Macklon NS, Geraedts JPM, Fauser BCJM. Conception to ongoing pregnancy: the “black box” of early pregnancy loss. Hum Reprod Update. 2002;8:333

Chang EJ, Bendikson K, Nguyen  BT. Advanced paternal age increases the risk of spontaneous abortion. Fertil Steril 2017; 108, Supplement: e104–e105

Magnus M.C., Wilcox A. J., Morken N-H., et al. Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. BMJ, 2019; 20;364

Nguyen BT,  Chang EJ, BendiksonKA. Advanced Paternal Age and the Risk of Spontaneous Abortion: An Analysis of the Combined 2011-2013 and 2013-2015 National Survey of Family Growth. Am J Obstet Gynecol; 2019 221(5):476.e1-476.e7.

 

“Freezing time” – Fertility preservation through oocyte and embryo freezing

Cryopreservation is an extremely useful technique of assisted reproduction, as it gives the opportunity to preserve cell viability for a very long period of time – theoretically forever – in liquid nitrogen at a temperature of -196 ^ο C, in order to be used in the future, essentially “freezing time”. In humans, this method was first used for the cryopreservation of spermatozoa – the first use of frozen/thawed human spermatozoa to achieve a pregnancy was done in 1953 – with very good results.

The birth in 1983 of the first two children from frozen/thawed embryo transfer, was an important development in in vitro fertilization, as it gave the opportunity to reduce the number of embryos transferred, while the supernumerary embryos could be frozen for future use. Cryopreserved embryos can be used if the fresh embryo transfer failed to produce a pregnancy or in couples with a successful pregnancy who later wish to have another child. Also, in women at high risk for the development of the ovarian hyperstimulation syndrome, all embryos can be frozen and embryo transfer is deferred to a subsequent cycle; recent studies have shown that, using this approach, the live birth rate is at least as good and probably higher, without any risk for the woman. The same approach can be used when the endometrial development is not optimal or when there are factors reducing the chances of embryo implantation and pregnancy, such as premature progesterone elevation.

Until recently, oocyte cryopreservation using the older techniques was not very successful. Nevertheless, the new method of ultra-rapid freezing, vitrification, was shown to be associated with excellent results in oocyte and embryo survival rates after thawing reaching 90% but also in pregnancy rates. This development made oocyte cryopreservation a viable option for fertility preservation.

This approach is utilized in women with cancer who wish, before undergoing chemo/radiotherapy, to freeze their oocytes in order to use them, after they are cured from their primary disease, to achieve a pregnancy. This approach is already been used since many years in men with similar problems, by freezing their sperm.

Oocyte cryopreservation is also offering women, who are not ready to have children, the opportunity to store their oocytes for future use. Studies have shown that the most important factor affecting woman’s fertility is her age; the optimal reproductive age for women is 20 to 30 years, when the highest fertility rates are observed, declining thereafter due to a progressive decrease in the number and quality of oocytes. However, in Greece, as in most western societies, the age at which women have their first child has been deferred by 10 to 15 years, approximately to the age of 35, with negative impact on their fertility. Thus, oocyte cryopreservation together with oral contraceptive pills, both promote the reproductive autonomy of women: the first by giving them the opportunity to defer the age of childbearing without negative consequences and the latter by allowing them to program the time of childbearing.

In conclusion, embryo cryopreservation represents an integral part of in vitro fertilization, as it increases the efficiency and safety of the procedure, while oocyte cryopreservation allows women to preserve their fertility for medical or social reasons.