Recent Advances in Infertility Management

Infertility is the failure to achieve a pregnancy after 12 months of regular, unprotected intercourse, and it is a problem of the couple, not of the woman alone. Recent advances in infertility management run along the whole pathway: sharper tests of sperm function, individualised IVF stimulation, laboratory techniques such as PICSI and EmbryoGlue, pre-implantation genetic testing, egg freezing and early work on ovarian rejuvenation.

Dr. Soma Singh, Associate Director - IVF & Infertility, Max Super Speciality Hospital, Noida, India, structured her masterclass for doctors across Africa around a simple principle: for every step of management, set the standard practice beside what has changed. This guide follows the same logic. It covers how infertility is defined and what causes it, the management pathway from history to assisted reproduction, and the questions that now dominate a fertility clinic: age, egg freezing, genetic testing of embryos and the safety of babies conceived through IVF. Three companion articles go deeper: the infertility workup, from history and examination to screening and diagnostic tests, male infertility evaluation, sperm DNA fragmentation and treatment, and the treatment ladder from lifestyle change through IUI, IVF, ICSI and PICSI.

How infertility is defined

Infertility is diagnosed when a couple has not conceived after one year of regular intercourse without contraception. Dr. Singh distinguishes two forms:

• Primary infertility: the couple has never had a pregnancy.
• Secondary infertility: the couple has had at least one pregnancy before, whether it ended in a miscarriage or a live birth.

The distinction matters clinically because a previous pregnancy proves that the system worked at some point, which shifts the search towards what has changed since: a new partner, a pelvic infection, surgery or simply age.

How common infertility is, and why the male partner matters

Dr. Singh put the prevalence of infertility at around 15%: of every ten couples, one or two will have difficulty conceiving. Her central message on causes was that infertility is a combined problem. In 30 to 35% of couples, male factors alone are responsible, and male factors contribute to almost half of all cases overall.

She broke the causes down as follows:

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital condition in which the uterus and upper vagina do not develop. PCOS, which Dr. Singh also called PCOD, is the commonest cause of irregular ovulation.

The practical consequence is that the male partner is evaluated from the first visit, not after months of tests on the woman. The evaluation Dr. Singh recommends for men is set out in the male infertility article.

When to investigate before 12 months

The one-year rule has exceptions. Dr. Singh investigates earlier when the woman is older than 35 or has irregular periods, a history suggesting pelvic infection or endometriosis, or previous ovarian surgery; when the man has known or suspected poor semen quality; and when either partner has had chemotherapy or radiotherapy, which can destroy germ cells. How that evaluation proceeds is set out in the infertility workup.

The management pathway at a glance

Dr. Singh's pathway runs in a fixed order, and each stage is covered in depth in a companion article.

1. Initial assessment. A detailed history from both partners, physical examination, then laboratory tests in two sets: screening tests for any couple planning a pregnancy, and diagnostic tests that find the cause. See the infertility workup.
2. Male evaluation. Semen analysis against World Health Organization (WHO) reference limits, then endocrine, urological and genetic evaluation and sperm function tests where indicated. See male infertility and sperm DNA fragmentation.
3. Lifestyle modification for both partners.
4. Medical management: ovulation-inducing drugs for the woman, and targeted hormonal treatment for a minority of men.
5. Fertility-enhancing surgery by hysteroscopy, laparoscopy or robotic surgery.
6. Assisted reproductive technology (ART): intrauterine insemination (IUI), in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI) and its refinements. See the assisted reproduction ladder.
7. Fertility preservation and rejuvenation therapies, which Dr. Singh described as the latest frontier of the field and which this guide covers below.

Recent advances in infertility management

Several developments separate current practice from the protocols many clinicians trained on. Dr. Singh highlighted these:

• Sperm DNA fragmentation testing. A normal semen analysis does not prove normal sperm function. Measuring the DNA fragmentation index explains some cases previously labelled unexplained and can redirect a couple from repeated IUI to ICSI.
• Tailor-made stimulation. IVF has moved from one-size-fits-all regimens to individualised protocols and doses, including dual stimulation (DuoStim), which collects eggs twice within one menstrual cycle for women with low ovarian reserve or little time.
• PICSI. Physiological ICSI uses a dish coated with hyaluronan to select mature sperm with better DNA integrity before injection.
• EmbryoGlue. A hyaluronan-rich transfer medium that Dr. Singh uses for couples with recurrent implantation failure.
• Pre-implantation genetic testing (PGT). Cells are taken from a day-five embryo and tested so that only chromosomally normal embryos are transferred.
• Cryopreservation. Freezing of eggs, sperm and embryos for cancer patients, for women with declining reserve and for women who choose to delay motherhood.
• Ovarian rejuvenation. Platelet-rich plasma (PRP) injected into the ovaries, still at an early, investigational stage.

How age affects fertility and miscarriage risk

Dr. Singh calls the woman's age the single most important factor deciding the success of any fertility treatment. Optimal female fertility lies between 20 and 30, and fertility declines as age advances. The duration of infertility matters too: the longer a couple has been trying, the lower their chance of conceiving, which she put at a fall of 20 to 25% with each year.

The decline is not only a matter of egg numbers. Two women of 40 can have very different ovarian reserves; a woman with PCOS may still have many eggs at that age. What falls for everyone is egg quality. With age, the meiotic spindle that separates chromosomes during egg maturation becomes dysfunctional, so a growing share of eggs carry the wrong number of chromosomes. An abnormal egg makes an abnormal embryo, which either fails to implant or miscarries.

Dr. Singh gave the miscarriage risk by maternal age:

The risk rises further after 45, when about 95% of pregnancies with the woman's own eggs end in miscarriage. Couples in this age group must be told plainly that even a successful conception with their own eggs may end in miscarriage.

Age affects the uterus as well as the egg. Dr. Singh noted that studies show endometrial receptivity declines after about 44, even when a donor egg is used. Her summary was that the biological clock runs independently of chronological age, and the right time to build a family is earlier rather than later. She added one counterpoint: a woman who has only started trying at 41 or 42, with a short duration of infertility, can still produce good results, whereas a woman who has tried for many years without conceiving may have an additional problem such as poor endometrial receptivity.

Medical fitness before pregnancy after 35

Clinically, a woman above 35 is of advanced reproductive age, however young she is in general terms. Before helping such a woman conceive, Dr. Singh treats a medical fitness assessment as mandatory, beyond the routine screening tests: liver and kidney function tests, a thorough cardiac check-up, blood sugar and blood pressure, and cervical screening by Pap smear or liquid-based cytology. Diabetes or hypertension must be controlled before she conceives.

Egg freezing and fertility preservation

Freezing eggs, sperm or embryos preserves fertility for people who would otherwise lose it. Dr. Singh's centre offers it for three groups:

• Young people with cancer or a precancerous condition who must undergo chemotherapy or radiotherapy. Preserving eggs or sperm beforehand may be their only option for a biological child.
• Women with threatened ovarian function: premature ovarian failure from a genetic cause, planned ovarian surgery, or already reduced ovarian reserve.
• Women who choose to delay motherhood, whether because they have not yet found a partner or want to establish their careers first. Because age is the dominant factor in success, freezing eggs at a younger age protects the quality of the eggs she will later use.

Where time before cancer treatment is short, dual stimulation within a single cycle can maximise the number of eggs collected, a protocol described in the assisted reproduction article.

Pre-implantation genetic testing (PGT) of embryos

PGT tests embryos before transfer so that only those with a normal chromosome pattern (euploid embryos) are placed in the uterus. The embryo is grown to the blastocyst stage on day five, when it has an inner cell mass, which becomes the baby, and an outer layer of trophectoderm cells, which becomes the placenta. A few trophectoderm cells are removed and tested.

Dr. Singh uses PGT in two situations:

• Carrier couples. When both partners carry the same inherited condition, such as thalassaemia trait or a sickle cell gene picked up by routine haemoglobin electrophoresis, PGT screens the embryos so that an affected embryo is not transferred.
• Advanced maternal age. When the woman is older than about 38 to 40, the rising rate of chromosomal abnormality makes it worthwhile to select a normal embryo, provided she has enough ovarian reserve to grow embryos to day five. Randomised trials have not shown that testing embryos for chromosome number raises the cumulative live birth rate per started cycle, and ESHRE does not recommend it for routine use; its main benefit is fewer failed transfers and miscarriages.

Ovarian rejuvenation with PRP

For older women keen to use their own eggs, Dr. Singh's centre has begun injecting platelet-rich plasma into the ovaries. She was explicit about its status: it does not reverse ageing, some women have benefited, papers claiming a benefit are emerging, and more data are needed. Ovarian PRP remains an experimental treatment, and professional bodies do not recommend it outside research settings.

Donor eggs and pregnancy after menopause

A woman who has reached menopause has no eggs that can be retrieved, but she can still carry a pregnancy using a donor egg. The missing ovarian hormones are given from outside to prepare the uterine lining, a donor egg is fertilised and the embryo transferred. Dr. Singh's centre does this routinely, including for women who reach menopause young. Her observation on headline-making late pregnancies was direct: a woman who conceives at 45 or 46 has almost certainly used a donor egg.

Are babies born through IVF healthy?

Dr. Singh's answer to the commonest question from couples is that babies born through ART carry no significant increase in congenital anomalies compared with naturally conceived babies. The first IVF baby was born in 1978, and, as she noted, evidence from meta-analyses has been accumulating ever since. Where higher risks appear, she attributes them to the parents' age rather than the procedure: a fair comparison is with naturally conceiving couples of the same age. Meta-analyses do report a small increase in the relative risk of birth defects after ART, much of it linked to the parents' underlying infertility and age rather than to the laboratory technique.

The next frontier: eggs and sperm from a person's own cells

The longer-term horizon is laboratory-made gametes. Dr. Singh noted that normal-looking sperm and eggs have been produced from skin cells and stem cells in research settings and tested in animals. Whether such sperm can fertilise normally is still being worked out. If the work succeeds, couples who now need donor eggs or sperm may one day use gametes made from their own cells.

Where to go next

The questions the audience raised, on haemoglobin electrophoresis, retrograde ejaculation, oligospermia, embryo transfer risks and pregnancy after menopause, are answered in the Live Discussion from this masterclass. For other angles on the same field, Dr. Hrishikesh Pai's guide to the WHO infertility guidelines sets out the global recommendations, and Dr. Shelly Singh's guide to pre-IVF workups and corrective surgery covers preparing a couple for IVF. Costs for treatment at partner hospitals are summarised on the IVF and fertility treatment cost page, and related specialists are listed under obstetrics and gynaecology.